Detailed characterization of the complex mitochondrial pathophysiology of DLD-1–deficient C. elegans provided evidence to link DLD deficiency with a broader constellation of mitochondrial pathophysiology, including a dramatically increased mitochondrial stress response, an adaptive mitochondrial proliferation, and marked ATP deficiency, despite normal RC enzyme activities and integrated mitochondrial RC capacity at the level of mitochondrial membrane potential. The gene discussed is RGN; the disease is pyruvate dehydrogenase E3 deficiency.