{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:25:51Z","timestamp":1787851551914,"version":"build-2784847793"},"reference-count":149,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Research Project of the Jiangxi Provincial Department of Education","award":["GJJ2401828"],"award-info":[{"award-number":["GJJ2401828"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Aging mesenchymal stem\/stromal cells (MSCs) lose regenerative capacity as redox imbalance, mitochondrial damage, defective organelle quality control and chronic inflammation converge. Yet these processes are commonly considered in isolation, obscuring whether damaged mitochondrial cargo reaches lysosomes and is ultimately degraded. Here, we define mitochondria\u2013lysosome quality flux (MLQF) as an author-proposed, evidence-graded framework that tracks mitochondrial damage from recognition and sorting through lysosomal delivery to terminal lysosomal degradation in aging MSCs. The framework explicitly separates delivery to an acidic compartment from completed degradation and distinguishes direct MSC evidence from cross-model mechanisms and candidate pathways. MSC studies most strongly support macroautophagy-dependent mitophagy, particularly when assessed using dynamic flux reporters. By contrast, mitochondria-derived vesicles and microautophagy-like or piecemeal routes remain incompletely validated in MSCs. Studies in non-MSC systems further show that mitochondria\u2013lysosome contact sites can support lysosomal acidification, although their contribution to natural MSC aging remains unresolved. By locating rate-limiting defects across this continuum, MLQF provides a testable basis for linking incomplete mitochondrial clearance to inflammatory signaling, lineage drift and regenerative decline, and for selecting bottleneck-matched interventions.<\/jats:p>","DOI":"10.3390\/cells15171548","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:47:13Z","timestamp":1787849233000},"page":"1548","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondria\u2013Lysosome Quality Flux in Aging Mesenchymal Stem\/Stromal Cells: Quality-Control Bottlenecks and Therapeutic Opportunities for Regenerative Decline"],"prefix":"10.3390","volume":"15","author":[{"given":"Lingling","family":"Cheng","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaojie","family":"Song","sequence":"additional","affiliation":[{"name":"Jiangxi Provincial Key Laboratory of Cell Precision Therapy, School of Basic Medical Sciences, Jiujiang University, Jiujiang 332005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13036-023-00361-9","article-title":"Clinical utility of mesenchymal stem\/stromal cells in regenerative medicine and cellular therapy","volume":"17","author":"Maldonado","year":"2023","journal-title":"J. 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