Turn your mito ON! – Harnessing Light Energy to Rewire Metabolism During Aging

Metabolism uses carbon sources in the form of metabolites to fuel mitochondrial energyproduction. Mitochondria are the cellular powerhouses and much like pollution from coal burningpower plants, produce toxic metabolic intermediates and reactive oxygen species whilegenerating energy. Subsequently, metabolic enzymes and mitochondria accumulate damageand become dysfunctional with age. In organisms from C. elegans to humans, metabolismdeclines with age. Rejuvenating energy production has therapeutic promise to promotelongevity however, translating model organism findings has been limiting.We propose to transform how humans transduce energy. We will convert the cellular coalburning power plant to solar power and provide an energy transduction pathway that bypassesage-damaged metabolic pathways and prevents the formation of reactive intermediates.Rejuvenating mitochondrial function using a light-activated tool called mitochondria-ON issufficient to increase adult C. elegans lifespan (PMID:36873708). We will translate this leap inaging research to humans by constructing a new version of this validated approach that isamendable to the complexities of human tissue. Can we harness the energy of light to treat age-associated vision loss? Can we eventually upgrade mtON to function in inner organs?