PKC Downregulation Upon Rapamycin Treatment Attenuates Mitochondrial Disease

In a study from December 14, 2020, researchers discovered that the beneficial effects of rapamycin treatment in a mouse model of Leigh syndrome, a fatal neurometabolic disorder caused by mitochondrial dysfunction, are due to the downregulation of protein kinase C (PKC). The study involved Ndufs4 knock-out (KO) mice, and the team found that rapamycin not only restored mitochondrial protein levels but also inhibited signaling through mTOR complexes and reduced the abundance and activity of multiple PKC isoforms. Furthermore, administering PKC inhibitors to these mice increased their survival, delayed neurological deficits, prevented hair loss, and decreased inflammation, suggesting that PKC could be a potential therapeutic target for severe mitochondrial diseases.