Boon Seng Soh

A*STAR Institute of Molecular and Cell Biology, Singapore

Mitochondrial dysfunction underlies a broad spectrum of inherited and age-related  disorders.  In  mitochondrial  encephalomyopathy,   lactic acidosis,   and   stroke-like    episodes   (MELAS),    mutations   in   the mitochondrial genome impair energy production and cellular function. We show that introducing healthy donor mitochondria into  MELAS endothelial  cells  enhances  metabolic  activity  and  reduces  mutant mitochondrial DNA load, leading to measurable functional recovery. These improvements are accompanied by increased protein translation

and restored energy metabolism. Building on these findings, we applied mitochondrial therapy to a SIRT6 knockdown model of induced pluripotent stem cell (iPSC)-derived cardiomyocytes to simulate cardiac  aging. The transfer  of healthy  mitochondria  attenuated  aging  phenotypes, improved  mitochondrial  respiration,  and  strengthened  contractile  performance.  Collectively, these results highlight the potential of mitochondrial therapy to rejuvenate cellular function and provide  a  promising  approach  to  treating  both  genetic  and  age-related  mitochondrial dysfunction.