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Increasing evidence in recent years indicates that mitochondria are not only central to cellular metabolism but also play a pivotal role in regulating apoptosis. However, no systematic review elucidating how mitochondria finely regulate apoptotic processes through multidimensional mechanisms, including apoptosis\u2010resistant diseases such as cancer. This paper systematically summarizes the molecular mechanisms by which mitochondria mediate apoptosis. We focus on the regulation of cytochrome\n                    <jats:italic>c<\/jats:italic>\n                    (Cyt c) release by the Bcl\u20102 protein family and the activation of downstream caspase cascades. Furthermore, we provide an in\u2010depth analysis of intrinsic factors, including mitochondrial structural remodeling (membrane rupture, cristae remodeling, and membrane lipid redistribution), dynamics imbalance (fusion, fission, and mitophagy), and mitochondrial DNA abnormalities, as well as extrinsic factors involving interorganelle interactions with the endoplasmic reticulum, lysosomes, and other organelles. Additionally, we review clinical and preclinical advances in drugs targeting these pathways. This review aims to provide a comprehensive perspective on the complex network of mitochondrial regulation of apoptosis and offer valuable insights for developing novel clinical therapeutic strategies for cancer and other diseases.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70911","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:28:07Z","timestamp":1787729287000},"source":"Crossref","is-referenced-by-count":0,"title":["Mitochondria as the Hub of Apoptosis: A Comprehensive Insight From Mitochondria to Interactions With Other Organelles"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1513-5616","authenticated-orcid":false,"given":"Rubin","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Physiology School of Basic Medical Sciences Southwest Medical University  Luzhou China"},{"name":"Department of Cardiology Institute of Cardiovascular Research the Affiliated Hospital Southwest 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