Mitochondria-Localized Nestin Protects Mesenchymal Stem Cells from Senescence by Maintaining Cristae Structure and Function.

ABSTRACT: Nestin, a well-characterized intermediate filament protein expressed in stem cells, is increasingly recognized for its non-canonical roles in diverse subcellular compartments. Here, a novel mitochondrial localization of Nestin in human mesenchymal stem cells (hMSCs) is identified, where it functions as a critical protector against mitochondrial dysfunction and cellular senescence. It is demonstrated that Nestin is imported into the mitochondrial intermembrane space via its N-terminal mitochondrial targeting sequence through Translocase of the Outer Mitochondrial Membrane 20 (TOM20)-dependent machinery. Within mitochondria, Nestin directly interacts with Mic60 to maintain cristae architecture and sustain oxidative phosphorylation. Genetic ablation of mitochondrial Nestin triggers cristae di

SUBMITTER: Chen H 

PROVIDER: S-EPMC12697773 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature