Mitophagy in Relation to Chronic Inflammation/ROS in Aging

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2024 Jun 4

PMID 38834837

Authors

Liang Kong

Shuhao Li

Yu Fu

Qinyun Cai

Xinyun Du

Jingyan Liang

Tan Ma

Affiliations

Soon will be listed here.

Abstract

Various assaults on mitochondria occur during the human aging process, contributing to mitochondrial dysfunction. This mitochondrial dysfunction is intricately connected with aging and diseases associated with it. In vivo, the accumulation of defective mitochondria can precipitate inflammatory and oxidative stress, thereby accelerating aging. Mitophagy, an essential selective autophagy process, plays a crucial role in managing mitochondrial quality control and homeostasis. It is a highly specialized mechanism that systematically removes damaged or impaired mitochondria from cells, ensuring their optimal functioning and survival. By engaging in mitophagy, cells are able to maintain a balanced and stable environment, free from the potentially harmful effects of dysfunctional mitochondria. An ever-growing body of research highlights the significance of mitophagy in both aging and age-related diseases. Nonetheless, the association between mitophagy and inflammation or oxidative stress induced by mitochondrial dysfunction remains ambiguous. We review the fundamental mechanisms of mitophagy in this paper, delve into its relationship with age-related stress, and propose suggestions for future research directions.

Citing Articles

Non high density lipoprotein to high density lipoprotein cholesterol ratio and type 2 diabetes in Middle aged and Elderly Chinese.

Tan J, Zhu H, Zeng Y, Li J, Zhao Y, Xiao X Sci Rep. 2025; 15(1):8485.

PMID: 40074743 PMC: 11903779. DOI: 10.1038/s41598-024-84686-5.

Small-vessel-disease-induced white matter damage in occipital lobe epilepsy.

Kim J, Lee D, Lee H, Park K Front Neurol. 2025; 16:1538598.

PMID: 40007738 PMC: 11850237. DOI: 10.3389/fneur.2025.1538598.

References

Guo J, Huang X, Dou L, Yan M, Shen T, Tang W . Aging and aging-related diseases: from molecular mechanisms to interventions and treatments. Signal Transduct Target Ther. 2022; 7(1):391. PMC: 9755275. DOI: 10.1038/s41392-022-01251-0. View

Sun Y, Cao Y, Wan H, Memetimin A, Cao Y, Li L . A mitophagy sensor PPTC7 controls BNIP3 and NIX degradation to regulate mitochondrial mass. Mol Cell. 2023; 84(2):327-344.e9. DOI: 10.1016/j.molcel.2023.11.038. View

Yu C, Davidson S, Harapas C, Hilton J, Mlodzianoski M, Laohamonthonkul P . TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS. Cell. 2020; 183(3):636-649.e18. PMC: 7599077. DOI: 10.1016/j.cell.2020.09.020. View

Wang Y, Li N, Zhang X, Horng T . Mitochondrial metabolism regulates macrophage biology. J Biol Chem. 2021; 297(1):100904. PMC: 8294576. DOI: 10.1016/j.jbc.2021.100904. View

Miwa S, Kashyap S, Chini E, von Zglinicki T . Mitochondrial dysfunction in cell senescence and aging. J Clin Invest. 2022; 132(13). PMC: 9246372. DOI: 10.1172/JCI158447. View

Amorim J, Coppotelli G, Rolo A, Palmeira C, Ross J, Sinclair D . Mitochondrial and metabolic dysfunction in ageing and age-related diseases. Nat Rev Endocrinol. 2022; 18(4):243-258. PMC: 9059418. DOI: 10.1038/s41574-021-00626-7. View

Ashrafi G, Schwarz T . The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ. 2012; 20(1):31-42. PMC: 3524633. DOI: 10.1038/cdd.2012.81. View

Jiang Y, Krantz S, Qin X, Li S, Gunasekara H, Kim Y . Caveolin-1 controls mitochondrial damage and ROS production by regulating fission - fusion dynamics and mitophagy. Redox Biol. 2022; 52:102304. PMC: 9018165. DOI: 10.1016/j.redox.2022.102304. View

Willemsen J, Neuhoff M, Hoyler T, Noir E, Tessier C, Sarret S . TNF leads to mtDNA release and cGAS/STING-dependent interferon responses that support inflammatory arthritis. Cell Rep. 2021; 37(6):109977. DOI: 10.1016/j.celrep.2021.109977. View

10.

Zhang T, Liu Q, Gao W, Sehgal S, Wu H . The multifaceted regulation of mitophagy by endogenous metabolites. Autophagy. 2021; 18(6):1216-1239. PMC: 9225590. DOI: 10.1080/15548627.2021.1975914. View

11.

Yamano K, Youle R . PINK1 is degraded through the N-end rule pathway. Autophagy. 2013; 9(11):1758-69. PMC: 4028335. DOI: 10.4161/auto.24633. View

12.

Yan C, Gong L, Chen L, Xu M, Abou-Hamdan H, Tang M . PHB2 (prohibitin 2) promotes PINK1-PRKN/Parkin-dependent mitophagy by the PARL-PGAM5-PINK1 axis. Autophagy. 2019; 16(3):419-434. PMC: 6999623. DOI: 10.1080/15548627.2019.1628520. View

13.

Samuvel D, Li L, Krishnasamy Y, Gooz M, Takemoto K, Woster P . Mitochondrial depolarization after acute ethanol treatment drives mitophagy in living mice. Autophagy. 2022; 18(11):2671-2685. PMC: 9629059. DOI: 10.1080/15548627.2022.2046457. View

14.

Puri R, Cheng X, Lin M, Huang N, Sheng Z . Mul1 restrains Parkin-mediated mitophagy in mature neurons by maintaining ER-mitochondrial contacts. Nat Commun. 2019; 10(1):3645. PMC: 6692330. DOI: 10.1038/s41467-019-11636-5. View

15.

Di Rita A, Peschiaroli A, D Acunzo P, Strobbe D, Hu Z, Gruber J . HUWE1 E3 ligase promotes PINK1/PARKIN-independent mitophagy by regulating AMBRA1 activation via IKKα. Nat Commun. 2018; 9(1):3755. PMC: 6138665. DOI: 10.1038/s41467-018-05722-3. View

16.

Orvedahl A, Sumpter Jr R, Xiao G, Ng A, Zou Z, Tang Y . Image-based genome-wide siRNA screen identifies selective autophagy factors. Nature. 2011; 480(7375):113-7. PMC: 3229641. DOI: 10.1038/nature10546. View

17.

Alan P, Vandevoorde K, Joshi B, Cardoen B, Gao G, Mohammadzadeh Y . Basal Gp78-dependent mitophagy promotes mitochondrial health and limits mitochondrial ROS. Cell Mol Life Sci. 2022; 79(11):565. PMC: 9596570. DOI: 10.1007/s00018-022-04585-8. View

18.

Lazarou M, Sliter D, Kane L, Sarraf S, Wang C, Burman J . The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature. 2015; 524(7565):309-314. PMC: 5018156. DOI: 10.1038/nature14893. View

19.

Richter B, Sliter D, Herhaus L, Stolz A, Wang C, Beli P . Phosphorylation of OPTN by TBK1 enhances its binding to Ub chains and promotes selective autophagy of damaged mitochondria. Proc Natl Acad Sci U S A. 2016; 113(15):4039-44. PMC: 4839414. DOI: 10.1073/pnas.1523926113. View

20.

Heo J, Ordureau A, Paulo J, Rinehart J, Harper J . The PINK1-PARKIN Mitochondrial Ubiquitylation Pathway Drives a Program of OPTN/NDP52 Recruitment and TBK1 Activation to Promote Mitophagy. Mol Cell. 2015; 60(1):7-20. PMC: 4592482. DOI: 10.1016/j.molcel.2015.08.016. View