AbstractPulmonary fibrosis is a chronic interstitial lung disease with no curative therapeutic treatment, leading to significant mortality. The aims of this study were to investigate the regulatory mechanisms of mitophagy in the progression of pulmonary fibrosis. Through bioinformatics analysis, we identified the downregulation of long-chain fatty acyl-CoA synthetase 1 (ACSL1) as being associated with the severity of pulmonary fibrosis.

摘要肺纤维化是一种慢性间质性肺病，没有治愈的治疗方法，导致严重的死亡率。本研究的目的是研究线粒体自噬在肺纤维化进展中的调节机制。通过生物信息学分析，我们确定长链脂肪酰基辅酶A合成酶1（ACSL1）的下调与肺纤维化的严重程度有关。

A pulmonary fibrosis model was established through bleomycin (BLM) exposure both in vivo and in vitro. Mitoquinone (MitoQ) pretreatment significantly decreased redox damage, stabilized mitochondrial membrane potential (MMP), improved mitochondrial dynamics, and activated PINK1/Parkin-mediated mitophagy, thereby alleviating pulmonary fibrosis.

通过体内和体外博来霉素（BLM）暴露建立肺纤维化模型。Mitoquinone（MitoQ）预处理显着降低氧化还原损伤，稳定线粒体膜电位（MMP），改善线粒体动力学，并激活PINK1/Parkin介导的线粒体自噬，从而减轻肺纤维化。

In vitro, overexpression of ACSL1 mitigated mitochondrial damage and restored PINK1/Parkin-mediated mitophagy under BLM exposure. In contrast, ACSL1 inhibition exacerbated pulmonary fibrosis, and these adverse effects could not be reversed by MitoQ treatment. Taken together, our study reveals a novel mechanism underlying the pathogenesis of pulmonary fibrosis and suggests a potential therapeutic target for its treatment..

在体外，ACSL1的过表达减轻了线粒体损伤，并在BLM暴露下恢复了PINK1/Parkin介导的线粒体自噬。相反，ACSL1抑制加剧了肺纤维化，MitoQ治疗无法逆转这些不良反应。综上所述，我们的研究揭示了肺纤维化发病机制的新机制，并为其治疗提供了潜在的治疗靶点。。

IntroductionPulmonary fibrosis is characterized as a chronic, progressive interstitial lung disease that leads to airway contraction and ultimately respiratory failure1,2. Clinically, it presents as progressive dyspnea and deterioration in lung function. Recent epidemiological studies indicate that the incidence of pulmonary fibrosis is on the rise, with a median survival of approximately 3–5 years after diagnosis1,3.

引言肺纤维化的特征是慢性进行性间质性肺病，导致气道收缩并最终导致呼吸衰竭1,2。临床上，它表现为进行性呼吸困难和肺功能恶化。最近的流行病学研究表明，肺纤维化的发病率正在上升，诊断后的中位生存期约为3-5年1,3。

Multiple risk factors, including smoking, environmental exposure, viral infections, and genetic predispositions, have been identified as high-risk contributors to pulmonary fibrosis4. Unfortunately, no current medications have been shown to effectively inhibit or reverse pulmonary fibrosis. Exploring the exact pathogenesis of pulmonary fibrosis should be contributed to provide a novel target for disease control.Mitochondrial dysfunction, characterized by insufficient energy production by the mitochondria, is believed to play a significant role in the development and progression of various diseases, including pulmonary fibrosis5,6.

包括吸烟，环境暴露，病毒感染和遗传易感性在内的多种风险因素已被确定为肺纤维化的高危因素4。不幸的是，目前还没有药物可以有效抑制或逆转肺纤维化。探索肺纤维化的确切发病机制应有助于为疾病控制提供新的靶点。线粒体功能障碍的特征是线粒体产生的能量不足，据信在包括肺纤维化在内的各种疾病的发展和进展中起着重要作用5,6。

Mitophagy, a form of selective autophagy, is crucial for maintaining mitochondrial quality control by removing damaged or dysfunctional mitochondria7,8,9. Insufficient mitophagy is associated with the pathological states of pulmonary fibrosis, particularly in aging lungs8,10,11. Impaired mitophagy leads to the accumulation of dysfunctional mitochondria, overproduction of reactive oxygen species (ROS), and alterations in mitochondrial dynamics, which contribute to oxidative stress and fibrotic processes7.

线粒体自噬是一种选择性自噬，通过去除受损或功能失调的线粒体7,8,9来维持线粒体质量控制至关重要。线粒体自噬不足与肺纤维化的病理状态有关，特别是在衰老的肺中8,10,11。线粒体自噬受损导致功能失调的线粒体积累，活性氧（ROS）的过量产生以及线粒体动力学的改变，这有助于氧化应激和纤维化过程7。

There are various signaling mechanisms regulated mitophagy, with PTEN-induced putative kinase 1 (PINK1) and E3 ubiquitin ligase Parkin (Parkin) mediated mitophagy characterized as a key pathway in these mechanisms12. Deficiency i.

有多种信号传导机制调节线粒体自噬，PTEN诱导的推定激酶1（PINK1）和E3泛素连接酶Parkin（Parkin）介导的线粒体自噬是这些机制的关键途径12。缺陷i。

Data availability

数据可用性

The original data presented in the study are included in the manuscript/Supplementary Material. Further inquiries can be directed to the corresponding author.

研究中提供的原始数据包含在手稿/补充材料中。进一步的询问可以直接联系通讯作者。

ReferencesMoss, B. J., Ryter, S. W. & Rosas, I. O. Pathogenic mechanisms underlying idiopathic pulmonary fibrosis. Annu. Rev. Pathol. Mech. Dis. 17, 515–546 (2022).Article

参考文献Moss，B.J.，Ryter，S.W。和Rosas，I.O。特发性肺纤维化的致病机制。年。Pathol牧师。机械。。17515-546（2022）。文章

Google Scholar

谷歌学者

Hill, C. & Wang, Y. Autophagy in pulmonary fibrosis: friend or foe? Genes Dis. 9, 1594–1607 (2022).Article

Hill，C。＆Wang，Y。肺纤维化中的自噬：朋友还是敌人？基因Dis。91594-1607（2022）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Luppi, F., Kalluri, M., Faverio, P., Kreuter, M. & Ferrara, G. Idiopathic pulmonary fibrosis beyond the lung: understanding disease mechanisms to improve diagnosis and management. Respir Res. 22, 109 (2021).Article

Luppi，F.，Kalluri，M.，Faverio，P.，Kreuter，M。＆Ferrara，G。肺外特发性肺纤维化：了解疾病机制以改善诊断和管理。Respir Res.22109（2021）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Gandhi, S., Tonelli, R., Murray, M., Samarelli, A. V. & Spagnolo, P. Environmental causes of idiopathic pulmonary fibrosis. Int. J. Mol. Sci. 24, 16481 (2023).Article

Gandhi，S.，Tonelli，R.，Murray，M.，Samarelli，A.V。＆Spagnolo，P。特发性肺纤维化的环境原因。Int.J.Mol.Sci。2416481（2023）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Prakash, Y. S., Pabelick, C. M. & Sieck, G. C. Mitochondrial dysfunction in airway disease. Chest. 152, 618–626 (2017).Article

Prakash，Y.S.，Pabelick，C.M。和Sieck，G.C。气道疾病中的线粒体功能障碍。胸部。152618-626（2017）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Rangarajan, S., Bernard, K. & Thannickal, V. J. Mitochondrial dysfunction in Pulmonary Fibrosis. Ann. Am. Thorac. Soc. 14, S383–S388 (2017).Article

Rangarajan，S.，Bernard，K。＆Thannickal，V.J。肺纤维化中的线粒体功能障碍。安。上午。胸部。Soc.14，S383–S388（2017）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ding, W. X., Yin, X. M. & Mitophagy Mechanisms, pathophysiological roles, and analysis. Biol. Chem. 393, 547–564 (2012).Article

丁，W.X.，尹，X.M。＆Mitophagy机制，病理生理作用和分析。生物化学。393547-564（2012）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Albano, G. D., Montalbano, A. M., Gagliardo, R. & Profita, M. Autophagy/Mitophagy in Airway diseases: impact of oxidative stress on epithelial cells. Biomolecules. 13, 1217 (2023).Article

Albano，G.D.，Montalbano，A.M.，Gagliardo，R。＆Profita，M。气道疾病中的自噬/线粒体自噬：氧化应激对上皮细胞的影响。生物分子。131217（2023）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Larson-Casey, J. L., He, C. & Carter, A. B. Mitochondrial quality control in pulmonary fibrosis. Redox Biol. 33, 101426 (2020).Article

Larson Casey，J.L.，He，C。＆Carter，A.B。肺纤维化中的线粒体质量控制。氧化还原生物。33101426（2020）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Cala-Garcia, J. D., Medina-Rincon, G. J., Sierra-Salas, P. A., Rojano, J. & Romero, F. The role of mitochondrial dysfunction in idiopathic pulmonary fibrosis: New perspectives for a Challenging Disease. Biology. 12, 1237 (2023).Article

Cala-Garcia，J.D.，Medina-Rincon，G.J.，Sierra Salas，P.A.，Rojano，J。＆Romero，F。线粒体功能障碍在特发性肺纤维化中的作用：一种具有挑战性的疾病的新观点。生物学。121237（2023）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Sharma, A., Ahmad, S., Ahmad, T., Ali, S. & Syed, M. A. Mitochondrial dynamics and mitophagy in lung disorders. Life Sci. 284, 119876 (2021).Article

Sharma，A.，Ahmad，S.，Ahmad，T.，Ali，S。＆Syed，M.A。肺疾病中的线粒体动力学和线粒体自噬。生命科学。284119876（2021）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Tsubouchi, K., Araya, J. & Kuwano, K. PINK1-PARK2-mediated mitophagy in COPD and IPF pathogeneses. Inflamm. Regen. 38, 18 (2018).Article

Tsubouchi，K.，Araya，J。＆Kuwano，K。PINK1-PARK2介导的COPD和IPF发病机制中的线粒体自噬。发炎。再生。38,18（2018）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Bueno, M. et al. PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis. J. Clin. Invest. 125, 521–538 (2015).Article

Bueno，M。等人。PINK1缺乏会损害线粒体稳态并促进肺纤维化。J、 临床。。125521-538（2015）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Kobayashi, K. et al. Involvement of PARK2-mediated mitophagy in idiopathic pulmonary fibrosis pathogenesis. J. Immunol. 197, 504–516 (2016).Article

Kobayashi，K。等人。PARK2介导的线粒体自噬参与特发性肺纤维化发病机制。J、 免疫。197504-516（2016）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Li, Y. et al. MitoQ ameliorates PM2.5-induced pulmonary fibrosis through regulating the mitochondria DNA homeostasis. Chemosphere. 330, 138745 (2023).Article

Li，Y。等人MitoQ通过调节线粒体DNA稳态来改善PM2.5诱导的肺纤维化。化学球。330138745（2023）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Chu, L. et al. Tetrandrine alleviates pulmonary fibrosis by inhibiting alveolar epithelial cell senescence through PINK1/Parkin-mediated mitophagy. Eur. J. Pharmacol. 969, 176459 (2024).Article

Chu，L。等人。粉防己碱通过PINK1/Parkin介导的线粒体自噬抑制肺泡上皮细胞衰老来减轻肺纤维化。欧洲药理学杂志。969176459（2024）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Sivakumar, P. et al. RNA sequencing of transplant-stage idiopathic pulmonary fibrosis lung reveals unique pathway regulation. ERJ Open. Res. 5, 00117–2019 (2019).Article

Sivakumar，P。等人。移植期特发性肺纤维化肺的RNA测序揭示了独特的途径调控。ERJ打开。第500117-2019（2019）号决议。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yang, I. V. et al. Expression of cilium-associated genes defines novel molecular subtypes of idiopathic pulmonary fibrosis. Thorax. 68, 1114–1121 (2013).Article

Yang，I.V.等人。纤毛相关基因的表达定义了特发性肺纤维化的新分子亚型。胸部。681114-1121（2013）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Deng, X. et al. Identification of 4 autophagy-related genes in heart failure by bioinformatics analysis and machine learning. Front. Cardiovasc. Med. 11, 1247079 (2024).Article

Deng，X。等人。通过生物信息学分析和机器学习鉴定心力衰竭中的4个自噬相关基因。正面。心血管。医学111247079（2024）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Rath, S. et al. MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations. Nucleic Acids Res. 49, D1541–D1547 (2021).Article

Rath，S。等人。MitoCarta3.0：一种更新的线粒体蛋白质组，现在具有亚细胞器定位和途径注释。核酸研究49，D1541–D1547（2021）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Habermann, A. C. et al. Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis. Sci. Adv. 6, eaba1972 (2020).Article

Habermann，A.C.等人。单细胞RNA测序揭示了不同上皮和间充质谱系在肺纤维化中的促纤维化作用。科学。《eaba1972》（2020）第6期。文章

ADS

广告

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Morse, C. et al. Proliferating SPP1/MERTK-expressing macrophages in idiopathic pulmonary fibrosis. Eur. Respir J. 54, 1802441 (2019).Article

Morse，C。等人。在特发性肺纤维化中增殖表达SPP1/MERTK的巨噬细胞。《欧洲呼吸杂志》541802441（2019）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Neumark, N., Cosme, C., Rose, K. A. & Kaminski, N. The idiopathic pulmonary fibrosis cell atlas. Am. J. Physiol. Lung Cell. Mol. Physiol. 319, L887–L893 (2020).Article

Neumark，N.，Cosme，C.，Rose，K.A。＆Kaminski，N。特发性肺纤维化细胞图谱。Am.J.Physiol。肺细胞。分子生理学。319，L887–L893（2020）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Della Latta, V., Cecchettini, A., Del Ry, S. & Morales, M. A. Bleomycin in the setting of lung fibrosis induction: from biological mechanisms to counteractions. Pharmacol. Res. 97, 122–130 (2015).Article

Della Latta，V.，Cecchettini，A.，Del Ry，S。＆Morales，M.A。博来霉素在肺纤维化诱导中的作用：从生物学机制到抵消作用。药理学。第97122-130号决议（2015年）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Moeller, A., Ask, K., Warburton, D., Gauldie, J. & Kolb, M. The bleomycin animal model: a useful tool to investigate treatment options for idiopathic pulmonary fibrosis? Int. J. Biochem. Cell Biol. 40, 362 (2008).Article

Moeller，A.，Ask，K.，Warburton，D.，Gauldie，J。＆Kolb，M。博来霉素动物模型：研究特发性肺纤维化治疗选择的有用工具？Int.J.生物化学。细胞生物学。40362（2008）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Percie, D. et al. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol. 18, e3000410 (2020).Article

Percie，D.等人，《ARRIVE指南2.0：报告动物研究的更新指南》。《公共科学图书馆·生物学》。18，e3000410（2020）。文章

Google Scholar

谷歌学者

Weng, A. B., Deng, M. M., Liu, X. D., Wang, H. B. & Lin, Q. MitoQ alleviated PM2.5 induced pulmonary epithelial cells injury by inhibiting mitochondrial-mediated apoptosis. Iran. J. Public. Health. 53, 614–624 (2024).PubMed

Weng，A.B.，Deng，M.M.，Liu，X.D.，Wang，H.B。＆Lin，Q。MitoQ通过抑制线粒体介导的细胞凋亡减轻PM2.5诱导的肺上皮细胞损伤。伊朗。J、 公众。健康。53614-624（2024）。PubMed出版社

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Roca-Portoles, A. & Tait, S. W. G. Mitochondrial quality control: from molecule to organelle. Cell. Mol. Life Sci. 78, 3853–3866 (2021).Article

Roca-Portoles，A.＆Tait，S.W.G.线粒体质量控制：从分子到细胞器。细胞。分子生命科学。783853-3866（2021）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Chen, W., Zhao, H. & Li, Y. Mitochondrial dynamics in health and disease: mechanisms and potential targets. Sig Transduct. Target. Ther. 8, 333 (2023).Article

Chen，W.，Zhao，H。＆Li，Y。健康和疾病中的线粒体动力学：机制和潜在目标。信号传输。目标。他们。8333（2023）。文章

Google Scholar

谷歌学者

Love, M. I., Huber, W. & Anders, S. Moderated estimation of Fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).Article

Love，M.I.，Huber，W。＆Anders，S。用DESeq2缓和了RNA-seq数据的倍数变化和分散估计。基因组生物学。15550（2014）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ritchie, M. E. et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).Article

。核酸研究43，e47（2015）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Li, H. et al. The mitochondria-targeted antioxidant MitoQ ameliorates inorganic arsenic-induced DCs/Th1/Th2/Th17/Treg differentiation partially by activating PINK1-mediated mitophagy in murine liver. Ecotoxicol. Environ. Saf. 277, 116350 (2024).Article

Li，H。等人。线粒体靶向抗氧化剂MitoQ通过激活PINK1介导的小鼠肝脏线粒体自噬来部分改善无机砷诱导的DC/Th1/Th2/Th17/Treg分化。生态毒性。环境。南非。277116350（2024）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Dou, S. Y. et al. MitoQ inhibits hepatic stellate cell activation and liver fibrosis by enhancing PINK1/parkin-mediated mitophagy. Open Med. 16, 1718–1727 (2021).Article

Dou，S.Y.等人MitoQ通过增强PINK1/parkin介导的线粒体自噬来抑制肝星状细胞活化和肝纤维化。开放医学161718-1727（2021）。文章

Google Scholar

谷歌学者

Frangogiannis, N. Transforming growth factor-\(\:\beta\:\) in tissue fibrosis. J. Exp. Med. 217, e20190103 (2020).Kim, S. K., Jung, S. M., Park, K. S. & Kim, K. J. Integrative analysis of lung molecular signatures reveals key drivers of idiopathic pulmonary fibrosis. BMC Pulm Med. 21, 404 (2021).Article .

Frangogiannis，N。组织纤维化中的转化生长因子-（\：\ beta\：\）。J、 实验医学217，e20190103（2020）。Kim，S.K.，Jung，S.M.，Park，K.S。＆Kim，K.J。肺分子特征的综合分析揭示了特发性肺纤维化的关键驱动因素。BMC Pulm Med.21404（2021）。文章。

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Burman, J. L. et al. Mitochondrial fission facilitates the selective mitophagy of protein aggregates. J. Cell. Biol. 216, 3231–3247 (2017).Article

Burman，J.L.等人。线粒体裂变促进蛋白质聚集体的选择性线粒体自噬。J、 细胞。生物学2163231-3247（2017）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Parimon, T., Yao, C., Stripp, B. R., Noble, P. W. & Chen, P. Alveolar epithelial type II cells as drivers of lung fibrosis in idiopathic pulmonary fibrosis. Int. J. Mol. Sci. 21, 2269 (2020).Article

。Int.J.Mol.Sci。212269（2020）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Wu, H. et al. Progressive Pulmonary fibrosis is caused by elevated mechanical tension on alveolar stem cells. Cell. 180, 107–121e17 (2020).Article

Wu，H。等人。进行性肺纤维化是由肺泡干细胞的机械张力升高引起的。细胞。180107-121e17（2020）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Wang, Z. et al. Citrus alkaline extracts prevent endoplasmic reticulum stress in type II alveolar epithelial cells to ameliorate pulmonary fibrosis via the ATF3/PINK1 pathway. Phytomedicine. 89, 153599 (2021).Article

Wang，Z。等人。柑橘碱提取物通过ATF3/PINK1途径预防II型肺泡上皮细胞的内质网应激，以改善肺纤维化。植物医学。89153599（2021）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Khan, P. et al. Culture of human alveolar epithelial type II cells by sprouting. Respir Res. 19, 204 (2018).Article

Khan，P。等人。通过发芽培养人肺泡上皮II型细胞。Respir Res.19204（2018）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hara, H., Kuwano, K. & Araya, J. Mitochondrial quality control in COPD and IPF. Cells. 7, 86 (2018).Article

Hara，H.，Kuwano，K。和Araya，J。COPD和IPF中的线粒体质量控制。细胞。7,86（2018）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Youle, R. J. & van der Bliek, A. M. Mitochondrial fission, fusion, and stress. Science. 337, 1062–1065 (2012).Article

。科学。3371062-1065（2012）。文章

ADS

广告

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Thong, L., McElduff, E. J. & Henry, M. T. Trials and treatments: an update on Pharmacotherapy for Idiopathic Pulmonary Fibrosis. Life (Basel). 13, 486 (2023).ADS

Thong，L.，McElduff，E.J。＆Henry，M.T。试验和治疗：特发性肺纤维化药物治疗的最新进展。人寿保险（巴塞尔）。13486（2023）。广告

PubMed

PubMed

Google Scholar

谷歌学者

Pokharel, M. D. et al. Mitochondrial network dynamics in pulmonary disease: bridging the gap between inflammation, oxidative stress, and bioenergetics. Redox Biol. 70, 103049 (2024).Article

Pokharel，M.D.等人，《肺部疾病中的线粒体网络动力学：弥合炎症、氧化应激和生物能量学之间的差距》。氧化还原生物。70103049（2024）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yombo, D. J. K. et al. SEMA3B inhibits TGF\(\:\beta\:\)-induced extracellular matrix protein production and its reduced levels are associated with a decline in lung function in IPF. Am. J. Physiol. Cell. Physiol. 326, C1659–C1668 (2024).Salton, F., Volpe, M. C. & Confalonieri, M. Epithelial–mesenchymal transition in the Pathogenesis of Idiopathic Pulmonary Fibrosis.

Yombo，D。J。K。等人。SEMA3B抑制TGFβ诱导的细胞外基质蛋白产生，其水平降低与IPF肺功能下降有关。Am.J.Physiol。细胞。生理学。。Salton，F.，Volpe，M.C。＆Confalonieri，M。特发性肺纤维化发病机制中的上皮-间质转化。

Med. (Kaunas). 55, 83 (2019)..

和。55, 83 (2019)...

Google Scholar

谷歌学者

Gd, M. et al. Epithelial-Mesenchymal Transition (EMT): The Type-2 EMT in Wound Healing, Tissue Regeneration and Organ Fibrosis. Cells 10, (2021).Zhang, X. et al. Dissecting pulmonary fibroblasts heterogeneity in lung development, health and diseases. Heliyon. 9, e19428 (2023).Article .

Gd，M。等人。上皮-间质转化（EMT）：伤口愈合，组织再生和器官纤维化中的2型EMT。细胞10，（2021）。Zhang，X。等。解剖肺发育，健康和疾病中的肺成纤维细胞异质性。海伦。9，e19428（2023）。文章。

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hou, L. et al. MitoQ alleviates LPS-mediated acute lung injury through regulating Nrf2/Drp1 pathway. Free Radic Biol. Med. 165, 219–228 (2021).Article

Hou，L。等人MitoQ通过调节Nrf2/Drp1途径减轻LPS介导的急性肺损伤。自由基生物。医学165219-228（2021）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Zhao, C. et al. Long-term exposure to PM2.5 aggravates pulmonary fibrosis and acute lung injury by disrupting Nrf2-mediated antioxidant function. Environ. Pollut. 313, 120017 (2022).Article

Zhao，C.等人。长期暴露于PM2.5会通过破坏Nrf2介导的抗氧化功能而加重肺纤维化和急性肺损伤。环境。污染。313120017（2022）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Chen, L. et al. Mechanism of Yifei Decoction Combined with MitoQ on Inhibition of TGF\(\:\beta\:\)1/NOX4 and PDGF/ROCK Signal Pathway in Idiopathic Pulmonary Fibrosis. Evid Based Complement Alternat Med 6615615 (2021). (2021).Zhan, P. et al. Mitoquinone alleviates bleomycin-induced acute lung injury via inhibiting mitochondrial ROS-dependent pulmonary epithelial ferroptosis.

Chen，L。等。益肺汤联合MitoQ抑制特发性肺纤维化中TGFβ1/NOX4和PDGF/ROCK信号通路的机制。基于Evid的补体替代医学6615615（2021）。（2021年）。詹，P。等。米托醌通过抑制线粒体ROS依赖性肺上皮细胞凋亡来减轻博来霉素诱导的急性肺损伤。

Int. Immunopharmacol. 113, 109359 (2022).Article .

国际免疫药理学。113109359（2022）。文章。

PubMed

PubMed

Google Scholar

谷歌学者

Bingol, B. & Sheng, M. Mechanisms of mitophagy: PINK1, parkin, USP30 and beyond. Free Radic Biol. Med. 100, 210–222 (2016).Article

Bingol，B。＆Sheng，M。线粒体自噬的机制：PINK1，parkin，USP30及其后。自由基生物。医学100210-222（2016）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Weber, R. A. et al. Maintaining Iron Homeostasis is the key role of lysosomal acidity for cell proliferation. Mol. Cell. 77, 645–655e7 (2020).Article

维持铁稳态是溶酶体酸度对细胞增殖的关键作用。摩尔电池。77645-655e7（2020）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Gómez-Virgilio, L. et al. Autophagy: a Key Regulator of Homeostasis and Disease: an overview of Molecular mechanisms and modulators. Cells. 11, 2262 (2022).Article

Gómez-Virgilio，L。等人。自噬：体内平衡和疾病的关键调节剂：分子机制和调节剂概述。细胞。112262（2022）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ning, R. et al. The mitochondria-targeted antioxidant MitoQ attenuated PM2.5-induced vascular fibrosis via regulating mitophagy. Redox Biol. 46, 102113 (2021).Article

Ning，R。等人。线粒体靶向抗氧化剂MitoQ通过调节线粒体自噬来减轻PM2.5诱导的血管纤维化。氧化还原生物。46102113（2021）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zhou, Y. et al. ACSL1-Mediated Fatty Acid \(\:\beta\:\)-Oxidation Enhances Metastasis and Proliferation in Endometrial Cancer. Front. Biosci. (Landmark Ed). 29, 66 (2024).Quan, J., Bode, A. M. & Luo, X. ACSL family: the regulatory mechanisms and therapeutic implications in cancer. Eur.

Zhou，Y。等。ACSL1介导的脂肪酸（β）氧化增强子宫内膜癌的转移和增殖。正面。生物科学。（Landmark Ed）。29，66（2024）。Quan，J.，Bode，A.M。＆Luo，X。ACSL家族：癌症的调节机制和治疗意义。欧元。

J. Pharmacol. 909, 174397 (2021).Article .

J、 药理学。909174397（2021）。文章。

PubMed

PubMed

Google Scholar

谷歌学者

Ma, Y. et al. Long-chain fatty acyl-CoA synthetase 1 promotes prostate cancer progression by elevation of lipogenesis and fatty acid beta-oxidation. Oncogene. 40, 1806–1820 (2021).Article

Ma，Y。等人。长链脂肪酰基辅酶A合成酶1通过提高脂肪生成和脂肪酸β-氧化来促进前列腺癌的进展。致癌基因。401806-1820（2021）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ma, Y. et al. The diagnostic value of ACSL1, ACSL4, and ACSL5 and the clinical potential of an ACSL inhibitor in Non-small-cell Lung Cancer. Cancers (Basel). 16, 1170 (2024).Article

Ma，Y。等人。ACSL1，ACSL4和ACSL5的诊断价值以及ACSL抑制剂在非小细胞肺癌中的临床潜力。癌症（巴塞尔）。161170（2024）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Cao, Z. et al. ACSL1: a preliminary study that provides a new target for the treatment of renal fibrosis could bring new insights in diabetic kidney disease. Nefrologia (Engl Ed). 43 (Suppl 2), 38–46 (2023).Article

Cao，Z。et al。ACSL1：一项为治疗肾纤维化提供新靶点的初步研究可能为糖尿病肾病带来新的见解。Nefrologia（英语版）。43（补充2），38-46（2023）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Swigris, J. J. et al. Psychometric properties of the St George’s respiratory questionnaire in patients with idiopathic pulmonary fibrosis. Eur. Respir J. 49, 1601788 (2017).Article

Swigris，J.J.等人。特发性肺纤维化患者圣乔治呼吸问卷的心理测量学特性。《欧洲呼吸杂志》491601788（2017）。文章

PubMed

PubMed

Google Scholar

谷歌学者

Grevengoed, T. J., Cooper, D. E., Young, P. A., Ellis, J. M. & Coleman, R. A. Loss of long-chain acyl-CoA synthetase isoform 1 impairs cardiac autophagy and mitochondrial structure through mechanistic target of rapamycin complex 1 activation. FASEB J. 29, 4641–4653 (2015).Article

Grevengoed，T.J.，Cooper，D.E.，Young，P.A.，Ellis，J.M。＆Coleman，R.A。长链酰基辅酶A合成酶同工型1的丧失通过雷帕霉素复合物1激活的机制靶标损害心脏自噬和线粒体结构。FASEB J.294641–4653（2015）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zhao, L. et al. Defective fatty acid oxidation in mice with muscle-specific acyl-CoA synthetase 1 deficiency increases amino acid use and impairs muscle function. J. Biol. Chem. 294, 8819–8833 (2019).Article

Zhao，L。等人。肌肉特异性酰基辅酶A合成酶1缺乏症小鼠的脂肪酸氧化缺陷会增加氨基酸的使用并损害肌肉功能。J、 生物。化学。2948819-8833（2019）。文章

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Nan, J. et al. An Essential Role of the N-Terminal Region of ACSL1 in Linking Free Fatty Acids to Mitochondrial \(\:\beta\:\)-Oxidation in C2C12 Myotubes. Mol. Cells. 44, 637–646 (2021).Download referencesAcknowledgementsThe authors like to acknowledge the researchers at Key Laboratory of Translational Tumor Medicine in Fujian Province (Putian University, Putian, China) for their assistance with this study.FundingThis study was supported by Fujian Provincial Natural Science Foundation of China (No.

Nan，J。等人。ACSL1的N末端区域在将游离脂肪酸连接到C2C12肌管中的线粒体\（\：\β\）：\）氧化中的重要作用。摩尔细胞。44637-646（2021）。下载参考文献致谢作者感谢福建省转化肿瘤医学重点实验室（莆田大学，中国莆田）的研究人员对本研究的帮助。资助本研究得到福建省自然科学基金（No。

2024J011468, No. 2020J011251); the Fujian Health Provincial Technology Project, China (No. 2020GGA078); Medical Research Foundation of Putian University(No. 2024107).Author informationAuthors and AffiliationsDepartment of Pharmacy, The Affiliated Hospital of Putian University, Putian, ChinaQi LINPharmaceutical and Medical Technology College, Putian university, Putian, ChinaQi LIN, Yating LIN, Xinyan LIAO, Ziyi CHEN, Mengmeng DENG & Zhihao ZHONGKey Laboratory of Translational Tumor Medicine in Fujian Province, Putian University, Putian, ChinaQi LINAuthorsQi LINView author publicationsYou can also search for this author in.

2024J011468，编号2020J011251）；中国福建省卫生技术项目（编号2020GGA078）；莆田大学医学研究基金会（编号2024107）。作者信息作者和附属机构莆田大学附属医院药学系，莆田，中国麒麟制药与医学技术学院，莆田，中国麒麟，林亚婷，廖新燕，陈子怡，邓梦萌和赵浩中国莆田大学福建省转化肿瘤医学中重点实验室麒麟作者或麒麟观点作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarYating LINView author publicationsYou can also search for this author in

PubMed Google ScholarYating LINView作者出版物您也可以在

PubMed Google ScholarXinyan LIAOView author publicationsYou can also search for this author in

PubMed Google ScholarZiyi CHENView author publicationsYou can also search for this author in

PubMed Google ScholarZiyi CHENView作者出版物您也可以在

PubMed Google ScholarMengmeng DENGView author publicationsYou can also search for this author in

PubMed Google ScholarmanMeng DENGView作者出版物您也可以在

PubMed Google ScholarZhihao ZHONGView author publicationsYou can also search for this author in

PubMed谷歌学者Zhihao ZHONGView作者出版物您也可以在

PubMed Google ScholarContributionsQ.L. and Y.L. performed most of the experiments, Z.C. and M.D. analyzed data, Y.L, Z.Z, X.L, and Z.C contributed to experiments. Q.L. designed experiments, supervised the study, and wrote the manuscript.Corresponding authorCorrespondence to

PubMed谷歌学术贡献。五十、 Y.L.进行了大部分实验，Z.C.和M.D.分析了数据，Y.L，Z.Z，X.L和Z.C为实验做出了贡献。Q、 L.设计实验，监督研究并撰写手稿。对应作者对应

Qi LIN.Ethics declarations

齐林.道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Ethics approval

道德认可

This study is performed in accordance with relevant guidelines and regulations. The animal experiments were conducted in accordance with ARRIVE 2.0 guidelines and were approved by the Ethics Committee of the Affiliated Hospital of Putian University (ID: 2024101).

这项研究是根据相关的指导方针和规定进行的。动物实验按照ARRIVE 2.0指南进行，并经莆田大学附属医院伦理委员会批准（ID:2024101）。

Conflict of interest

利益冲突

The authors declare no competing interests.

作者声明没有利益冲突。

Additional informationPublisher’s noteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Electronic supplementary materialBelow is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2Supplementary Material 3Supplementary Material 4Rights and permissions.

。电子补充材料流是指向电子补充材料的链接。补充材料1补充材料2补充材料3补充材料4权利和权限。

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.

开放获取本文是根据知识共享署名非商业性NoDerivatives 4.0国际许可证授权的，该许可证允许以任何媒介或格式进行任何非商业性使用，共享，分发和复制，只要您对原始作者和来源给予适当的信任，提供知识共享许可证的链接，并指出您是否修改了许可材料。

You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

根据本许可证，您无权共享源自本文或其部分的改编材料。本文中的图像或其他第三方材料包含在文章的知识共享许可证中，除非该材料的信用额度中另有说明。如果材料未包含在文章的知识共享许可中，并且您的预期用途不受法律法规的许可或超出许可用途，则您需要直接获得版权所有者的许可。

To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/..

要查看此许可证的副本，请访问http://creativecommons.org/licenses/by-nc-nd/4.0/..

Reprints and permissionsAbout this articleCite this articleLIN, Q., LIN, Y., LIAO, X. et al. ACSL1 improves pulmonary fibrosis by reducing mitochondrial damage and activating PINK1/Parkin mediated mitophagy.

转载和许可本文引用本文LIN，Q.，LIN，Y.，LIAO，X。等人。ACSL1通过减少线粒体损伤和激活PINK1/Parkin介导的线粒体自噬来改善肺纤维化。

Sci Rep 14, 26504 (2024). https://doi.org/10.1038/s41598-024-78136-5Download citationReceived: 17 July 2024Accepted: 29 October 2024Published: 03 November 2024DOI: https://doi.org/10.1038/s41598-024-78136-5Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

科学报告1426504（2024）。https://doi.org/10.1038/s41598-024-78136-5Download引文接收日期：2024年7月17日接受日期：2024年10月29日发布日期：2024年11月3日OI：https://doi.org/10.1038/s41598-024-78136-5Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供

KeywordsPulmonary fibrosisACSL1MitoQMitophagyPINk1/Parkin signaling pathway

关键词肺纤维化1 MitoqMitophagypink1/Parkin信号通路