We propose that a variety of mitochondrial disease-associated seizure disorders, including Leigh syndrome (MT-ATP6, MT-ND3, MT-ND5, SURF1, others), Alpers syndrome (POLG), mitochondrial tRNA synthetase syndromes (RARS2 and others), Rett syndrome (MECP2), and CDKL5 disorder, have different genetic lesions but share common underlying cellular pathologies, namely oxidative stress and ferroptosis. Here, POLG is linked to Alpers syndrome.