Taking the dysfunction of the mitochondrial-matrix-residing metabolic enzyme methylmalonyl-coenzyme A mutase (MMUT) as a paradigm of a mitochondrial disease causing kidney tubular damage, the purpose of this Review is to highlight the role of mitochondria, not only as an energy powerhouse but also as a hub for the signaling and homeostasis pathways. The gene discussed is MMUT; the disease is inborn mitochondrial metabolism disorder.