[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-438935-105":59,"doc-detail-438935-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","mitophagy-in-the-pathogenesis-and-management-of-disease","Mitophagy in the pathogenesis and management of disease","","Mitophagy is a selective macroautophagy program that removes damaged mitochondria via lysosomal degradation, helping maintain mitochondrial homeostasis under metabolic and environmental stress. Mitochondrial dysfunction is linked to aging and many diseases, and mitophagy integrates pathways controlling mitochondrial quality, including biogenesis, dynamics, proteostasis, and the mitochondrial unfolded protein response. This review outlines mitophagy mechanisms, focusing on ubiquitin-dependent and receptor-mediated signaling, and links them to disease pathogenesis while highlighting emerging therapeutic strategies targeting mitophagy.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/mitophagy-in-the-pathogenesis-and-management-of-disease/438935/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/mitophagy-in-the-pathogenesis-and-management-of-disease/438935.png","ImageObject",300,407,{"name":92,"@type":93},"Theodore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-05","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does mitophagy play in maintaining cellular homeostasis?","Question",{"text":112,"@type":113},"Mitophagy selectively eliminates damaged mitochondria through lysosomal degradation, supporting cellular adaptation to metabolic and environmental stresses.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What are the main types of mitophagy selectivity signals described in the review?",{"text":117,"@type":113},"The review describes “eat me” signals that are generated via ubiquitin-dependent mechanisms or receptor-mediated pathways to target mitochondria for degradation.",{"name":119,"@type":110,"acceptedAnswer":120},"How does ubiquitin-mediated mitophagy recruit the autophagy machinery?",{"text":121,"@type":113},"Ubiquitin chains conjugate to damaged mitochondria, recruiting autophagy receptor proteins and downstream autophagy components that form autophagosomes for lysosomal delivery.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},438935,1790717131,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},7971461740886,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","[www.nature.com/cr](www.nature.com/cr)  \nCell [Research](Research www.cell-research.com)[ www.cell-research.com](Research www.cell-research.com)  \nREVIEW ARTICLE OPEN   \nMitophagy in the pathogenesis and management of disease  \nQi Wang 1,3, Yu Sun 2,3, Terytty Yang Li 2 ✉ and Johan Auwerx 1 ✉  \n© The Author(s) 2026  \nINTRODUCTION  \nMitochondria are central metabolic hubs essential for cellular homeostasis. In addition to their well-known role as powerhouses of the cell, generating ATP through oxidative phosphorylation (OXPHOS), mitochondria also regulate fatty acid metabolism, 1 calcium homeostasis,2 reactive oxygen species (ROS) generation,3 innate immune signaling,4,5 and cell death,6 making them important signaling integration platforms.7–9 Maintaining mitochondrial integrity is crucial for cellular, tissue, and organismal health, as mitochondrial dysfunction is a shared feature of aging and numerous diseases.10, 11  \nUnlike other organelles, mitochondria originate from α -proteobacteria12, 13 that symbiotically evolved within eukaryotic cells. They retain vestiges of their bacterial genome, mitochondrial DNA (mtDNA),14 which encodes essential components of the electron transport chain (ETC) . However, most mitochondrial proteins (~1400) are nuclear encoded,15 requiring precise coordination between nuclear DNA (nDNA) and mtDNA to ensure proper mitochondrial function. This complex regulatory interplay subjects mitochondria to multiple levels of transcriptional, translational, and post-translational control, making them particularly susceptible to mitonuclear imbalance and proteotoxic stress.7,8  \nTo maintain homeostasis, mitochondria engage in dynamic quality-control processes, including biogenesis, mitochondrial dynamics (fission and fusion), proteostasis, and stress responses such as the mitochondrial unfolded protein response (UPRmt) .9, 16–18 When mitochondria sustain irreparable damage, degradation pathways are activated to prevent the accumulation of dysfunctional organelles. Mitophagy is a selective form of macroautophagy that serves as the primary mechanism for eliminating damaged mitochondria through the lysosome,  \nensuring cellular adaptation to metabolic and environmental stresses. Additional mitochondrial clearance pathways, including mitochondria-derived vesicles (MDVs),19,20 mitochondrial-derived structures positive for the outer mitochondrial membrane (SPOT),21 vesicles derived from the inner mitochondrial membrane (VDIMs),22 and mitochondrial disposal via mitocytosis,23 have also been identified. In this review, we summarize the mechanisms of mitophagy (Supplementary information, Table S1), discuss its role in disease pathogenesis, and explore emerging therapeutic strategies that target mitophagy to restore mitochondrial homeostasis.  \nMITOPHAGY PATHWAYS  \nMitophagy was first observed in the 1970s,24 but specific mitophagy pathways have only recently been characterized. The selective removal of damaged or superfluous mitochondria relies on “eat me” signals, generated either by ubiquitin (Ub)-dependent or receptor-mediated pathways. In the Ub-dependent pathway, ubiquitin chains are conjugated to damaged mitochondria to recruit autophagy receptor proteins and subsequent autophagy machinery. In the receptor-mediated pathway, mitochondriallylocalized receptor proteins directly engage with the autophagy machinery to initiate mitophagy. Regardless of the pathway, the targeted mitochondria are degraded by macroautophagy (hereafter autophagy), which involves the sequestration of cytoplasmic components by double-membrane autophagosomes that then deliver them to lysosomes for degradation.  \nUbiquitin-mediated mitophagy pathway  \nUbiquitination not only tags proteins for proteasomal degradation but also serves as a platform for recruiting the autophagy  \n1Laboratory of Integrative Systems Physiology, Interfaculty Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland. 2Shanghai Key Labo","cbCaipHkpbOSNiCS","https://ap.wps.com/l/cbCaipHkpbOSNiCS","pdf",3521828,27,"English","# Introduction\n## Mitochondria and cellular homeostasis\n## Quality control and selective mitochondrial clearance\n# Mitophagy Pathways\n## Overview of selectivity and degradation via macroautophagy\n## Ubiquitin-mediated mitophagy pathway\n# Box 1: Crosstalk between autophagy and ubiquitin–proteasome systems","[{\"question\":\"What role does mitophagy play in maintaining cellular homeostasis?\",\"answer\":\"Mitophagy selectively eliminates damaged mitochondria through lysosomal degradation, supporting cellular adaptation to metabolic and environmental stresses.\"},{\"question\":\"What are the main types of mitophagy selectivity signals described in the review?\",\"answer\":\"The review describes “eat me” signals that are generated via ubiquitin-dependent mechanisms or receptor-mediated pathways to target mitochondria for degradation.\"},{\"question\":\"How does ubiquitin-mediated mitophagy recruit the autophagy machinery?\",\"answer\":\"Ubiquitin chains conjugate to damaged mitochondria, recruiting autophagy receptor proteins and downstream autophagy components that form autophagosomes for lysosomal delivery.\"}]","Mitophagy in the pathogenesis and management of disease | PDF",1790686906,68]