Melatonin suppresses senescence-derived mitochondrial dysfunction in mesenchymal stem cells via the HSPA1L-mitophagy pathway.

ABSTRACT: Mesenchymal stem cells (MSCs) are a popular cell source for stem cell-based therapy. However, continuous ex vivo expansion to acquire large amounts of MSCs for clinical study induces replicative senescence, causing decreased therapeutic efficacy in MSCs. To address this issue, we investigated the effect of melatonin on replicative senescence in MSCs. In senescent MSCs (late passage), replicative senescence decreased mitophagy by inhibiting mitofission, resulting in the augmentation of mitochondrial dysfunction. Treatment with melatonin rescued replicative senescence by enhancing mitophagy and mitochondrial function through upregulation of heat shock 70 kDa protein 1L (HSPA1L). More specifically, we found that melatonin-induced HSPA1L binds to cellular prion protein (PrP^C ), resu

SUBMITTER: Lee JH 

PROVIDER: S-EPMC7059143 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature