The mitochondrial integrated stress response: A novel approach to anti-aging and pro-longevity

被引：4

作者：

Wang, Xiaoding ^{[1
]}

Zhang, Guangyu ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Div Cardiol,Dept Internal Med, 1095 Jiefang Ave, Wuhan 430030, Peoples R China

来源：

AGEING RESEARCH REVIEWS | 2025年 / 103卷

基金：

中国国家自然科学基金;

关键词：

Mitochondrial integrated stress response; FGF21; Aging; Longevity; UNFOLDED PROTEIN RESPONSE; OXIDATIVE STRESS; INSULIN-RESISTANCE; ENERGY-METABOLISM; PREVENTS OBESITY; PKR ACTIVATION; BODY-WEIGHT; GROWTH; FGF21; DYSFUNCTION;

D O I：

10.1016/j.arr.2024.102603

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The ISR is a cellular signaling pathway that responds to various physiological changes and types of stimulation. The mitochondrial integrated stress response (ISRmt) is a stress response specific to mitochondria which is initiated by eIF2 alpha phosphorylation and is responsive to mitochondrial stressors. The ISRmt triggers diverse metabolic responses reliant on activating transcription factor 4 (ATF4). The preliminary phases of ISRmt can provoke an adaptive stress response that antagonizes age-related diseases and promotes longevity. In this review, we provide an overview of the molecular mechanisms of the ISRmt, with a particular focus on its potential as a therapeutic target for age-related disease and the promotion of longevity.

引用

页数：10

共 121 条

[1] A Wars2 Mutant Mouse Model Displays OXPHOS Deficiencies and Activation of Tissue-Specific Stress Response Pathways [J].

Agnew, Thomas ;

Goldsworthy, Michelle ;

Aguilar, Carlos ;

Morgan, Anna ;

Simon, Michelle ;

Hilton, Helen ;

Esapa, Chris ;

Wu, Yixing ;

Cater, Heather ;

Bentley, Liz ;

Scudamore, Cheryl ;

Poulton, Joanna ;

Morten, Karl J. ;

Thompson, Kyle ;

He, Langping ;

Brown, Steve D. M. ;

Taylor, Robert W. ;

Bowl, Michael R. ;

Cox, Roger D. .

CELL REPORTS, 2018, 25 (12) :3315-+

[2] Mitochondrial and metabolic dysfunction in ageing and age-related diseases [J].

Amorim, Joao A. ;

Coppotelli, Giuseppe ;

Rolo, Anabela P. ;

Palmeira, Carlos M. ;

Ross, Jaime M. ;

Sinclair, David A. .

NATURE REVIEWS ENDOCRINOLOGY, 2022, 18 (04) :243-258

[3] Folding the Mitochondrial UPR into the Integrated Stress Response [J].

Anderson, Nadine S. ;

Haynes, Cole M. .

TRENDS IN CELL BIOLOGY, 2020, 30 (06) :428-439

[4] Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums [J].

Arnold, Steven E. ;

Arvanitakis, Zoe ;

Macauley-Rambach, Shannon L. ;

Koenig, Aaron M. ;

Wang, Hoau-Yan ;

Ahima, Rexford S. ;

Craft, Suzanne ;

Gandy, Sam ;

Buettner, Christoph ;

Stoeckel, Luke E. ;

Holtzman, David M. ;

Nathan, David M. .

NATURE REVIEWS NEUROLOGY, 2018, 14 (03) :168-181

[5] Protective Coupling of Mitochondrial Function and Protein Synthesis via the eIF2α Kinase GCN-2 [J].

Baker, Brooke M. ;

Nargund, Amrita M. ;

Sun, Tiffany ;

Haynes, Cole M. .

PLOS GENETICS, 2012, 8 (06)

[6] Mitochondrial dysfunction remodels one - carbon metabolism in human cells [J].

Bao, Xiaoyan Robert ;

Ong, Shao-En ;

Goldberger, Olga ;

Peng, Jun ;

Sharma, Rohit ;

Thompson, Dawn A. ;

Vafai, Scott B. ;

Cox, Andrew G. ;

Marutani, Eizo ;

Ichinose, Fumito ;

Goessling, Wolfram ;

Regev, Aviv ;

Carr, Steven A. ;

Clish, Clary B. ;

Mootha, Vamsi K. .

ELIFE, 2016, 5

[7] mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle [J].

Ben-Sahra, Issam ;

Hoxhaj, Gerta ;

Ricoult, Stephane J. H. ;

Asara, John M. ;

Manning, Brendan D. .

SCIENCE, 2016, 351 (6274) :728-733

[8] FGF21 Regulates Metabolism Through Adipose-Dependent and -Independent Mechanisms [J].

BonDurant, Lucas ;

Ameka, Magdalene ;

Naber, Meghan ;

Markan, Kathleen ;

Idiga, Sharon ;

Acevedo, Michael ;

Walsh, Susan ;

Ornitz, David ;

Potthoff, Matthew .

CELL METABOLISM, 2017, 25 (04) :935-+

[9] ATF3 represses PINK1 gene transcription in lung epithelial cells to control mitochondrial homeostasis [J].

Bueno, Marta ;

Brands, Judith ;

Voltz, Lauren ;

Fiedler, Kaitlin ;

Mays, Brenton ;

St Croix, Claudette ;

Sembrat, John ;

Mallampalli, Rama K. ;

Rojas, Mauricio ;

Mora, Ana L. .

AGING CELL, 2018, 17 (02)

[10] Brown Adipocytes Secrete GDF15 in Response to Thermogenic Activation [J].

Campderros, Laura ;

Moure, Ricardo ;

Cairo, Montserrat ;

Gavalda-Navarro, Aleix ;

Quesada-Lopez, Tania ;

Cereijo, Ruben ;

Giralt, Marta ;

Villarroyao, Joan ;

Villarroya, Francesc .

OBESITY, 2019, 27 (10) :1606-1616

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