In the skeletal muscle, mitochondrial dysfunction causes the development of insulin resistance in different ways: (1) by activating several protein kinases, such as Protein kinase C (PKC) or c-Jun N-terminal kinase (JNK), which inhibit IRS-1 signaling by phosphorylation; (2) by reducing the expression levels of IRS-1 [16]; and (3) by inducing ER stress through excessive cytosolic calcium levels [17]. The gene discussed is IRS1; the disease is Insulin resistance.