Vitiligo: Something Wrong With Mitochondria (energy producing “Factories” of a human cell) (For Professionals)

• Although still poorly understood, theories to the etiology of vitiligo are emerging. One of them is mitochondrial  dysfunctioning which would lead to oxydative stress and destruction of the melanocytes (pigment cells, unable to renew themselves). More precisely an increased Cyclosporin A-dependent ROS production, associated with a loss of membrane potential (Δψm), and defective Complex I proteins activity and expression in vitro and ex vivo was observed in melanocytes (as well as fibroblasts and lymphocytes)

Accordingly to the defective electron transport chain activity and pathological sensitivity to Complex I inhibitor, rotenone, the authors found in melanocytic cells:

• Energy Production Changes

1. Increase of Cell energy units of the cell [ATP (Adenosine 5′-triphosphate)]
2. A slight increase in lactate production
3. An increased mitochondrial mass as possible compensatory mechanism to ensure necessary amount of cellular energy (ATP)

• Alteration of Signalling Pathways

1. An over-expression of p53 with a subsequent activation of target genes including GAD45, p21 PML IGFBP3 at mRNA and protein level both in vitro and ex vivo.
2. An alteration of signal transduction pathways with hyperphosphorylated p38 and ERK (extracellular-signal-regulated kinase)  was associated with a defective response to growth factors.

• Cell membrane changes

1. GC-MS analyses of the membrane lipid constitution revealed an increased level of cholesterol and of lipid peroxidation products including oxysterol moieties.

• DNA (Deoxyribonucleic acid) proteins

1. DNA, transciption factors, mitochondrial DNA  as well as produced proteins in vitiligo suggest that mitochondria have a role to play in vitiligo pathogenesis.

Conclusion The authors conclude that significant metabolic alterations are present in vitiligo and that mitochondria can be the source of a continuous intracellular oxidative stress, which makes the vitiligo melanocyte prone to senescence or susceptibility to external injuries.

Comment

• This is a very interesting article suggesting that mitochondria play an essentiel role in the pathogenesis of vitiligo.
• This conclusion brings other questions.
• Indeed mitochondria are transmitted by the mother as the Ovum is of maternal origin.
• The fertilized zygote will lead to all the cells of the newborn.
• Therefore if mitochondria are of maternal origin, would vitiligo also be transmitted through the maternal route ?
• If not, would some types of vitiligo (Vulgaris, segmental….) be transmitted through maternal routes. In that case mitochondrial alterations would bring key developments in the understanding of the condition

Contributors:

Dr Christophe HSU – dermatologist. Geneva, Switzerland

Source of information: M Picardo, B Bellei, E Bastonini, D Kovacs, M Ottaviani and M Dell’Anna Lab Cutaneous Physiopathology & CIRM, San Gallicano Dermatologic Institute, Rome, Italy. Hidden players in vitiligo pathogenesis: Mitochondria?  International Investigative Dermatology (IID) 2013 – Edinburgh, United Kingdom