SIRT3 and mitochondrial DNA depletion syndrome: For instance, defects or polymorphisms in mitochondrial DNA, like mutations in the gene encoding mitochondrial isobutyryl-coA dehydrogenase or mitochondrial DNA depletion syndromes, can result in excessive lipid accumulation in hepatocytes and the loss of the sirtuin 3 mediator, which can lead to reduced resistance to oxidative stress, and these are some of the various mechanisms that can contribute to the pathology [254,255,256].