Mitochondria-associated programmed cell death as a therapeutic target for age-related disease.

Thanh T Nguyen, Shibo Wei, Thu Ha Nguyen, Yunju Jo, Yan Zhang, Wonyoung Park, Karim Gariani, Chang-Myung Oh, Hyeon Ho Kim, Ki-Tae Ha, Kyu Sang Park, Raekil Park, In-Kyu Lee, Minho Shong, Riekelt H Houtkooper, Dongryeol Ryu

Journal: Experimental & molecular medicine 2023;55(8):1595-1619

PMID: 37612409

Free Full Text on Nature Publishing Group View on PubMed

Abstract

Mitochondria, ubiquitous double-membrane-bound organelles, regulate energy production, support cellular activities, harbor metabolic pathways, and, paradoxically, mediate cell fate. Evidence has shown mitochondria as points of convergence for diverse cell death-inducing pathways that trigger the various mechanisms underlying apoptotic and nonapoptotic programmed cell death. Thus, dysfunctional cellular pathways eventually lead or contribute to various age-related diseases, such as neurodegenerative, cardiovascular and metabolic diseases. Thus, mitochondrion-associated programmed cell death-based treatments show great therapeutic potential, providing novel insights in clinical trials. This review discusses mitochondrial quality control networks with activity triggered by stimuli and that maintain cellular homeostasis via mitohormesis, the mitochondrial unfolded protein response, and mitophagy. The review also presents details on various forms of mitochondria-associated programmed cell death, including apoptosis, necroptosis, ferroptosis, pyroptosis, parthanatos, and paraptosis, and highlights their involvement in age-related disease pathogenesis, collectively suggesting therapeutic directions for further research.

Address: Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, 61005, Republic of Korea.; Department of Precision Medicine, Sungkyunkwan University School of Medicine, Suwon, 16419, Republic of Korea.; Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, 26426, Republic of Korea.; Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 16419, Republic of Korea.; Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, 50612, Republic of Korea.; Service of Endocrinology, Diabetes, Nutrition and Patient Therapeutic Education, Geneva University Hospitals, Geneva, 1205, Switzerland.; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, 06351, Republic of Korea.; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea.; Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea.; Laboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. [email protected].; Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. [email protected].; Amsterdam Cardiovascular Sciences, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. [email protected].; Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, 61005, Republic of Korea. [email protected].

DOI: 10.1038/s12276-023-01046-5

Link outs

Free resources

Full Text Sources:

MeSH Terms: Apoptosis, Mitochondria, Cell Death, Pyroptosis