Theoretical and Natural Science
- The Open Access Proceedings Series for Conferences
Theoretical and Natural Science
Vol. 29, 16 January 2024
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Mitochondria in aging: A review of structure, function, and interorganelle relationships
* Author to whom correspondence should be addressed.
Abstract
The process of aging is what everyone is experiencing during the whole life. Many factors contribute to the aging process, among which the changes in mitochondrial structure and function are one important step. in this review, we elaborated on the relationship between mitochondria and aging from three aspects: the structure and function of mitochondria, the changes of mitochondria during aging, and the relationship between mitochondria and other organelles, we also described the progress related to mitochondrial targeted therapy. In summary, The passage highlights a review that examines the connection between mitochondria and aging from three main angles: understanding the structure and function of mitochondria, exploring how mitochondria change as an individual ages, and uncovering their relationships with other cellular organelles. Additionally, the passage discusses the advancements in mitochondrial targeted therapy within the context of aging.
Keywords
Mitochondria, Aging, Cell senescence
References
1. Da Silva-Álvarez S, Picallos-Rabina P, Antelo-Iglesias L, et al. The development of cell senescence. Experimental Gerontology 2019; 128: 110742.
2. Salama R, Sadaie M, Hoare M, et al. Cellular senescence and its effector programs. Genes Dev 2014; 28: 99–114.
3. Campisi J, d’Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 2007; 8: 729–740.
4. Miwa S, Kashyap S, Chini E, et al. Mitochondrial dysfunction in cell senescence and aging. Journal of Clinical Investigation 2022; 132: e158447.
5. Hamasaki M, Furuta N, Matsuda A, et al. Autophagosomes form at ER–mitochondria contact sites. Nature 2013; 495: 389–393.
6. Walker BR, Moraes CT. Nuclear-Mitochondrial Interactions. Biomolecules 2022; 12: 427.
7. Hughes CE, Coody TK, Jeong M-Y, et al. Cysteine Toxicity Drives Age-Related Mitochondrial Decline by Altering Iron Homeostasis. Cell 2020; 180: 296-310.e18.
8. Sun N, Youle RJ, Finkel T. The Mitochondrial Basis of Aging. Molecular Cell 2016; 61: 654–666.
9. Bonora M, Patergnani S, Rimessi A, et al. ATP synthesis and storage. Purinergic Signalling 2012; 8: 343–357.
10. Shadel GS, Horvath TL. Mitochondrial ROS Signaling in Organismal Homeostasis. Cell 2015; 163: 560–569.
11. Quinlan CL, Perevoshchikova IV, Hey-Mogensen M, et al. Sites of reactive oxygen species generation by mitochondria oxidizing different substrates. Redox Biology 2013; 1: 304–312.
12. Schmeisser S, Priebe S, Groth M, et al. Neuronal ROS signaling rather than AMPK/sirtuin-mediated energy sensing links dietary restriction to lifespan extension. Molecular Metabolism 2013; 2: 92–102.
13. Picard M, Shirihai OS. Mitochondrial signal transduction. Cell Metabolism 2022; 34: 1620–1653.
14. Booth DM, Várnai P, Joseph SK, et al. Oxidative bursts of single mitochondria mediate retrograde signaling toward the ER. Molecular Cell 2021; 81: 3866-3876.e2.
15. Nacarelli T, Lau L, Fukumoto T, et al. NAD+ metabolism governs the proinflammatory senescence-associated secretome. Nat Cell Biol 2019; 21: 397–407.
16. Sun N, Youle RJ, Finkel T. The Mitochondrial Basis of Aging. Molecular Cell 2016; 61: 654–666.
17. Von Zglinicki T. Oxidative stress shortens telomeres. Trends in Biochemical Sciences 2002; 27: 339–344.
18. Sakamuri SSVP, Sure VN, Kolli L, et al. Glycolytic and Oxidative Phosphorylation Defects Precede the Development of Senescence in Primary Human Brain Microvascular Endothelial Cells. GeroScience 2022; 44: 1975–1994.
19. Miwa S, Jow H, Baty K, et al. Low abundance of the matrix arm of complex I in mitochondria predicts longevity in mice. Nat Commun 2014; 5: 3837.
20. Ramírez-Camacho I, Flores-Herrera O, Zazueta C. The relevance of the supramolecular arrangements of the respiratory chain complexes in human diseases and aging. Mitochondrion 2019; 47: 266–272.
21. Chen H, Chan DC. Mitochondrial dynamics-fusion, fission, movement, and mitophagy-in neurodegenerative diseases. Human Molecular Genetics 2009; 18: R169–R176.
22. Mitochondria form contact sites with the nucleus to couple prosurvival retrograde response. SCIENCE ADVANCES 2020; 16.
23. Wilson EL, Metzakopian E. ER-mitochondria contact sites in neurodegeneration: genetic screening approaches to investigate novel disease mechanisms. Cell Death Differ 2021; 28: 1804–1821.
24. Simon DK, Lin MT, Zheng L, et al. Somatic mitochondrial DNA mutations in cortex and substantia nigra in aging and Parkinson’s disease. Neurobiology of Aging 2004; 25: 71–81.
25. Trifunovic A, Hansson A, Wredenberg A, et al. Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci USA 2005; 102: 17993–17998.
26. Pinto M, Moraes CT. Mechanisms linking mtDNA damage and aging. Free Radical Biology and Medicine 2015; 85: 250–258.
27. Correia‐Melo C, Marques FD, Anderson R, et al. Mitochondria are required for pro‐ageing features of the senescent phenotype. The EMBO Journal 2016; 35: 724–742.
28. Rizza S, Cardaci S, Montagna C, et al. S -nitrosylation drives cell senescence and aging in mammals by controlling mitochondrial dynamics and mitophagy. Proc Natl Acad Sci USA; 115. Epub ahead of print 10 April 2018. DOI: 10.1073/pnas.1722452115.
29. Johnson SC. Nutrient Sensing, Signaling and Ageing: The Role of IGF-1 and mTOR in Ageing and Age-Related Disease. In: Harris JR, Korolchuk VI (eds) Biochemistry and Cell Biology of Ageing: Part I Biomedical Science. Singapore: Springer Singapore, pp. 49–97.
30. Yang W, Nagasawa K, Münch C, et al. Mitochondrial Sirtuin Network Reveals Dynamic SIRT3-Dependent Deacetylation in Response to Membrane Depolarization. Cell 2016; 167: 985-1000.e21.
31. Camacho-Pereira J, Tarragó MG, Chini CCS, et al. CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell Metabolism 2016; 23: 1127–1139.
32. Chini CCS, Peclat TR, Warner GM, et al. CD38 ecto-enzyme in immune cells is induced during aging and regulates NAD+ and NMN levels. Nat Metab 2020; 2: 1284–1304.
33. Covarrubias AJ, Kale A, Perrone R, et al. Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages. Nat Metab 2020; 2: 1265–1283.
34. Xu H, Guan N, Ren Y-L, et al. IP3R-Grp75-VDAC1-MCU calcium regulation axis antagonists protect podocytes from apoptosis and decrease proteinuria in an Adriamycin nephropathy rat model. BMC Nephrol 2018; 19: 140.
35. Bravo‐Sagua R, Parra V, López‐Crisosto C, et al. Calcium Transport and Signaling in Mitochondria. In: Terjung R (ed) Comprehensive Physiology. Wiley, pp. 623–634.
36. Brookes PS, Yoon Y, Robotham JL, et al. Calcium, ATP, and ROS: a mitochondrial love-hate triangle. American Journal of Physiology-Cell Physiology 2004; 287: C817–C833.
37. Müller M, Ahumada-Castro U, Sanhueza M, et al. Mitochondria and Calcium Regulation as Basis of Neurodegeneration Associated With Aging. Front Neurosci 2018; 12: 470.
38. Wiel C, Lallet-Daher H, Gitenay D, et al. Endoplasmic reticulum calcium release through ITPR2 channels leads to mitochondrial calcium accumulation and senescence. Nat Commun 2014; 5: 3792.
39. McHugh D, Gil J. Senescence and aging: Causes, consequences, and therapeutic avenues. Journal of Cell Biology 2018; 217: 65–77.
40. Chapman J, Fielder E, Passos JF. Mitochondrial dysfunction and cell senescence: deciphering a complex relationship. FEBS Letters 2019; 593: 1566–1579.
41. Davalli P, Mitic T, Caporali A, et al. ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases. Oxidative Medicine and Cellular Longevity 2016; 2016: 1–18.
42. Korolchuk VI, Miwa S, Carroll B, et al. Mitochondria in Cell Senescence: Is Mitophagy the Weakest Link? EBioMedicine 2017; 21: 7–13.
43. Miquel J, Economos AC, Fleming J, et al. Mitochondrial role in cell aging. Experimental Gerontology 1980; 15: 575–591.
44. Rowland AA, Voeltz GK. Endoplasmic reticulum–mitochondria contacts: function of the junction. Nat Rev Mol Cell Biol 2012; 13: 607–615.
45. Poston CN, Krishnan SC, Bazemore-Walker CR. In-depth proteomic analysis of mammalian mitochondria-associated membranes (MAM). Journal of Proteomics 2013; 79: 219–230.
46. Ziegler DV, Martin N, Bernard D. Cellular senescence links mitochondria-ER contacts and aging. Commun Biol 2021; 4: 1323.
47. Cieri D, Vicario M, Giacomello M, et al. SPLICS: a split green fluorescent protein-based contact site sensor for narrow and wide heterotypic organelle juxtaposition. Cell Death Differ 2018; 25: 1131–1145.
48. Kalia R, Wang RY-R, Yusuf A, et al. Structural basis of mitochondrial receptor binding and constriction by DRP1. Nature 2018; 558: 401–405.
49. Joseph A-M, Adhihetty PJ, Wawrzyniak NR, et al. Dysregulation of Mitochondrial Quality Control Processes Contribute to Sarcopenia in a Mouse Model of Premature Aging. PLoS ONE 2013; 8: e69327.
50. Rubinsztein DC, Mariño G, Kroemer G. Autophagy and Aging. Cell 2011; 146: 682–695.
51. Rassow J, Dekker PJT, Van Wilpe S, et al. The preprotein translocase of the mitochondrial inner membrane: function and evolution. Journal of Molecular Biology 1999; 286: 105–120.
52. Poyton RO, McEwen JE. CROSSTALK BETWEEN NUCLEAR AND MITOCHONDRIAL GENOMES. Annu Rev Biochem 1996; 65: 563–607.
53. Eisenberg-Bord M, Zung N, Collado J, et al. Cnm1 mediates nucleus–mitochondria contact site formation in response to phospholipid levels. Journal of Cell Biology 2021; 220: e202104100.
54. Marchi S, Pinton P. The mitochondrial calcium uniporter complex: molecular components, structure and physiopathological implications. The Journal of Physiology 2014; 592: 829–839.
55. Liu T, Yang N, Sidor A, et al. MCU Overexpression Rescues Inotropy and Reverses Heart Failure by Reducing SR Ca 2+ Leak. Circ Res 2021; 128: 1191–1204.
56. Giacomello M, Pellegrini L. The coming of age of the mitochondria–ER contact: a matter of thickness. Cell Death Differ 2016; 23: 1417–1427.
57. Wiel C, Lallet-Daher H, Gitenay D, et al. Endoplasmic reticulum calcium release through ITPR2 channels leads to mitochondrial calcium accumulation and senescence. Nat Commun 2014; 5: 3792.
58. Madreiter-Sokolowski CT, Thomas C, Ristow M. Interrelation between ROS and Ca2+ in aging and age-related diseases. Redox Biology 2020; 36: 101678.
59. Rubinsztein DC, Mariño G, Kroemer G. Autophagy and Aging. Cell 2011; 146: 682–695.
60. Park JT, Lee Y-S, Cho KA, et al. Adjustment of the lysosomal-mitochondrial axis for control of cellular senescence. Ageing Research Reviews 2018; 47: 176–182.
61. Simon DK, Lin MT, Zheng L, et al. Somatic mitochondrial DNA mutations in cortex and substantia nigra in aging and Parkinson’s disease. Neurobiology of Aging 2004; 25: 71–81.
62. Saki M, Prakash A. DNA damage related crosstalk between the nucleus and mitochondria. Free Radical Biology and Medicine 2017; 107: 216–227.
63. Tranah GJ. Mitochondrial–nuclear epistasis: Implications for human aging and longevity. Ageing Research Reviews 2011; 10: 238–252.
64. McCay CM, Crowell MF, Maynard LA. The Effect of Retarded Growth Upon the Length of Life Span and Upon the Ultimate Body Size. The Journal of Nutrition 1935; 10: 63–79.
65. Merry BJ. Oxidative stress and mitochondrial function with aging - the effects of calorie restriction. Aging Cell 2004; 3: 7–12.
66. Kim Y, Triolo M, Hood DA. Impact of Aging and Exercise on Mitochondrial Quality Control in Skeletal Muscle. Oxidative Medicine and Cellular Longevity 2017; 2017: 1–16.
67. Hidalgo-Gutiérrez A, González-García P, Díaz-Casado ME, et al. Metabolic Targets of Coenzyme Q10 in Mitochondria. Antioxidants 2021; 10: 520.
68. KC S, Càrcamo JM, Golde DW. Vitamin C enters mitochondria via facilitative glucose transporter 1 (Gluti) and confers mitochondrial protection against oxidative injury. FASEB j 2005; 19: 1657–1667.
69. Fernandez-Marcos PJ, Auwerx J. Regulation of PGC-1α, a nodal regulator of mitochondrial biogenesis. The American Journal of Clinical Nutrition 2011; 93: 884S-890S.
Data Availability
The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.
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- Volume Title
- Proceedings of the 2nd International Conference on Modern Medicine and Global Health
- ISBN (Print)
- 978-1-83558-279-4
- ISBN (Online)
- 978-1-83558-280-0
- Published Date
- 16 January 2024
- Series
- Theoretical and Natural Science
- ISSN (Print)
- 2753-8818
- ISSN (Online)
- 2753-8826
- DOI
- 10.54254/2753-8818/29/20240749
- Copyright
- 16 January 2024
- Open Access
- This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited