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

Table 2

Genetic diseases displaying OS/MDF hallmarks.

Genetic diseases	OS/MDF-related Endpoints	References
Cancer-prone and/or early ageing diseases
Ataxia-telangiectasia	↑ ROS production; abnormal mt structure; ↓ΔΨ; ↑ mt enzymes; ↓ mitophagy	[35–39]
Bloom syndrome	↑ ROS production; antioxidant sensitive; ↑ WBC 8-OHdG	[40–42]
Cockayne syndrome	↓ OGG1; ↑ ROS production; ↑ DNA oxidative damage; ↑ mitophagy	[43–46]
	defective CSA and CSB localize to mt →↓ interaction with mt OGG1
Down syndrome	↑ ROS production; affected mt structure; defective Complex I activity;	[47–52]
	↓ CoQ10 lymphocyte and platelet levels; sensitive to CoQ10
Fanconi anaemia	↑ ROS production; ↑ 8-OHdG; ↓ GSH:GSSG; ↑ methylglyoxal; antioxidant	[54–60]
	sensitive; redox functions of FANC proteins; downregulation of antioxidant,
	chelating and stress proteins; ↓ ATP; ↓ΔΨ; ↓ Prdx3; abnormal mt structure
Hutchinson-Gilford syndrome	↑ ROS production; ↑ SOD-2 transcript; ↓ ATP content; ↓ caspase-like	[61, 62]
	proteasome activity; NAC sensitive
Nijmegen breakage syndrome	PARP hyperactivation and ↑ ROS production; ↓ mt p53 translocation	[63, 64]
Rothmund-Thomson syndrome	RECQL4 response to OS; RECQL4 interaction with PARP-1 and p53	[65–67]
Werner Syndrome	WRN regulates HIF-1 activation inducing mt ROS; ↑ OS; abnormal mt structure	[68–72]
Xeroderma pigmentosum	↓ repair of cyclo-dA; ↑ lipid peroxidation and protein glycation; ↓ CoQ serum levels;	[73–77]
	defective mt gene transcripts for 16 S rRNA, ATPase 6L and lactate dehydrogenase
Neurological and muscle genetic diseases
Adrenoleukodystrophy	↑ mtDNA oxidation and impaired OXPHOS; ↓ complex V; ↓ GSH; ↑ GSSG	[78–82]
	↓ total antioxidant defenses in symptomatic but not in asymptomatic patients;
	mitochondrial inner membrane potential dissipation; ↓ ATP
	ATP/ADP ratio; abnormal mt ultrastructure; dysregulated Fe metabolism
Duchenne Muscular Dystrophy	↑ protein thiol oxidation; ↑ lipofuscin; ↑ 4-hydroxynonenal; ↑ total hydroperoxides;	[83–85]
	uncoupled OXPHOS; ↓ maximal ATP synthesis; ↓ 𝛾-glutamyl cysteine ligase and GSH
Friedreich Ataxia	↓ complex I, II and III; ↓ aconitase; ↓ CoQ10 and Vit E; ↓ Fe-S cluster	[86–88]
	biosynthesis; mt Fe overload and cellular Fe dysregulation; ↑ sensitivity to OS
Huntington’s Disease	CoQ10-induced ↓ brain protein carbonyls; ↑ NADPH oxidase (NOX) activity in	[89–92]
	human HD brains; CoQ10 + creatine exert additive neuroprotective effects in HD mice and rats
Other Genetic Diseases
Hyperhomocysteinaemia	↑ MDA levels and carbonyl formation; ↓ sulfhydryl groups and total antioxidant	[93–95]
	status; ↓ΔΨ; release of cytochrome-c; ↑ mt matrix metalloproteinase
Sickle Cell Disease	↑ ROS production; ↑ advanced glycation end products (AGEs); ↓ GSH Iron-laden mt in WBC	[96–98]
Thalassaemia	Non-transferrin-bound iron (NTBI) → damage to mitochondria, lysosomes,	[99–101]
	lipid membranes, proteins, and DNA; ↑ WBC 8-OHdG; ↓ΔΨ; ↓ carnitine