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For instance, mutations in mtDNA-encoded Complex I genes like MT-ND1 cause Leigh syndrome, while in HF, Complex I and IV activity drops by 3050% in failing hearts [8]

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Targeting HIF-1 has therapeutic potential, but general inhibition should be avoided because HIF-1 has a the protective effect on mitochondria by reducing mitochondrial electron leakage and mito-stress (329)