SLC25A39: A Guardian against Cadmium-Induced Pleiotropic Disruption of Mitochondrial Homeostasis in Rat Neuronal Cells

Le résumé fourni par la source

Cadmium (Cd) is a neurotoxic heavy metal, and mitochondrial homeostasis disruption is a key mechanism underlying its neurotoxicity. SLC25A39, a mitochondrial transporter, maintains the mitochondrial homeostasis. This study investigated the role of SLC25A39 in the Cd-induced disruption of mitochondrial homeostasis in rat neuronal cells. The results revealed that Cd exposure markedly upregulated the SLC25A39 protein levels in neuronal cells. SLC25A39 deficiency further aggravated Cd-induced mitochondrial oxidative-stress-related abnormalities, including mitochondrial glutathione (mtGSH) depletion, elevated lipid peroxidation, mitochondrial reactive oxygen species (mtROS) accumulation, and reduced mitochondrial SOD2 protein levels. Moreover, SLC25A39 deficiency aggravated Cd-induced mitochondrial dysfunction, suppressed biogenesis, disrupted the dynamic balance, and hyperactivated mitophagy. Notably, DRP1 inhibition suppressed the Cd-induced upregulation of Pink1 and Parkin in SLC25A39-deficient PC12 cells. Collectively, SLC25A39 confers resistance to Cd-induced pleiotropic mitochondrial injuries, including oxidative stress, dysfunction, impaired biogenesis, dynamic imbalance, and excessive mitophagy. In PC12 cells, SLC25A39 may limit excessive mitophagy by negatively regulating the DRP1 activity.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.