Overexpression of mitochondrial oxodicarboxylate carrier (ODC1) preserves oxidative phosphorylation in a yeast model of Barth syndrome.

摘要: ABSTRACT Cardiolipin (CL) is a diglycerol phospholipid mostly found in mitochondria where it optimizes numerous processes, including oxidative phosphorylation (OXPHOS). To function properly, CL needs to be unsaturated, which requires the acyltransferase tafazzin. Loss-of-function mutations this protein are responsible for Barth syndrome (BTHS), presumably because of diminished OXPHOS capacity. Here, we show that overexpressing Odc1p, conserved oxodicarboxylic acid carrier located mitochondrial inner membrane, fully restores yeast model (taz1Δ) BTHS. The rescuing activity involves recovery normal expression key components sustain phosphorylation, cytochrome c and electron transport chain complexes IV III, strongly downregulated taz1Δ yeast. Interestingly, overexpression Odc1p was also shown previously rescue models diseases caused by defects assembly ATP synthase MPV17 result hepatocerebral DNA depletion syndrome. These findings define acids across membrane as potential therapeutic target large spectrum diseases,