Oxidative Stress and Mitochondrial Dysfunction across Broad-Ranging Pathologies: Toward Mitochondria-Targeted Clinical Strategies

Table 1

Mitochondrial dysfunction (MDF) and/or oxidative stress (OS) in some selected mitochondrial diseases.

	MDF/OS endpoints	References
Primary mitochondrial DNA-related diseases
Leber’s hereditary optic neuropathy (LHON)	mtDNA point mutations; Idebenone- and EPI-743-induced protection	[9–11]
Leigh syndrome, subacute necrotizing encephalomyelopathy	mtDNA point mutations; EPI-743-induced protection	[12]
Neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP)	↓ ATP synthase activity, ↑ ROS; ↑ p66Shc; phosphorylation; antioxidants-induced protection	[13, 14]
Mitochondrial myopathy, encephalomyopathy, lactic acidosis,; stroke-like symptoms (MELAS)	mtDNA Point Mutations; ↓ Complex I, III And IV,; ↑ Free radicals in CSF, CoQ10-induced protection	[15–19]
Myoclonic epilepsy with ragged red fibers (MERRF)	mtDNA point mutations; ↓ ATP, ↑ Matrix metallo-proteinase 1; ↑ ROS, ↑ carbonylated mt proteins	[20, 21]
Maternally inherited diabetes mellitus and deafness (MIDD)	mtDNA point mutations; CoQ10-induced protection	[22]
Kearns-Sayre syndrome (KSS)	mtDNA deletions; ↑ Myoglobin and antioxidant enzymes; mtDNA deletions with cyt-c oxidase-deficient cells and; loss of mitochondrial respiratory chain subunits	[23]
Chronic progressive external ophthalmoplegia (CPEO)	mtDNA deletions and point mutations; ↓ Complex I; and IV; ↑ OS biomarkers; tetracycline-induced; antioxidant protection	[24, 25]
Pearson syndrome	mtDNA deletions; ↓ OXPHOS, iron overload	[26, 27]
Secondary mitochondrial DNA-related diseases
Alpers-Huttenlocher Syndrome	Pol 𝛾 mutations; ↓ OXPHOS; mtDNA deletions/depletion	[28–31]
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)	Thymidine phosphorylase mutation; mtDNA deletions; ↓ CoQ10 levels	[32, 33]