UVC-induced mitochondrial degradation via autophagy correlates with mtDNA damage removal in primary human fibroblasts.

Abstract

Mitochondrial DNA (mtDNA) is more susceptible than nuclear DNA to helix-distorting damage via exposure to environmental genotoxins, partially due to a lack of nucleotide excision repair. Thus, this damage is irreparable and persistent in mtDNA in the short term. We recently found that helix-distorting mtDNA damage induced by ultraviolet C radiation (UVC) is gradually removed in Caenorhabditis elegans and that removal is dependent upon autophagy and mitochondrial dynamics. We here report the effects of UVC exposure on mitophagy, mitochondrial morphology, and indicators of mitochondrial function in mammalian cells. Exposure to UVC induced autophagy within 24 h; nonetheless, significant mitochondrial degradation was not observed until 72 h post exposure. Mitochondrial mass, morphology, and function were not significantly altered. These data further support the idea that persistent mtDNA damage is removed by autophagy and also suggest a powerful compensatory capacity for dealing with mtDNA damage.