Abstract
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, a maternally inherited mitochondrial disorder, is characterized by its genetic, biochemical and clinical complexity. The most common mutation associated with MELAS syndrome is the mtDNA A3243G mutation in the MT-TL1 gene encoding the mitochondrial tRNA-leu(UUR), which results in impaired mitochondrial translation and protein synthesis involving the mitochondrial electron transport chain complex subunits, leading to impaired mitochondrial energy production. Angiopathy, either alone or in combination with nitric oxide (NO) deficiency, further contributes to multi-organ involvement in MELAS syndrome. Management for MELAS syndrome is amostly symptomatic multidisciplinary approach. In this article, we review the clinical presentations, pathogenic mechanisms and options for management of MELAS syndrome.
Highlights
The inner boundary membrane (IBM) is adjacent to the outer membrane, whereas the cristae membrane (CM) is the protruding part of the IBM that invaginates into the matrix space, which encompasses diverse enzymes, ribosomes, transfer RNAs, and mitochondrial DNA (Figure 1B) [5]
The missense mutation maps to a conserved residue in the MT-TL1 gene coding for transfer RNAs (tRNAs)-leu(UUR), which is presumably used to impair the synthesis of mitochondrial protein [51].Apart from MELAS syndrome, the phenotypes associated to the mitochondrial DNA (mtDNA) A3243Gmutation are variable between patients, including neurological and nonneurological presentations which range from asymptomatic carriers to severe phenotypes; mtDNA A3243G accounts for approximately 80% of the causative mutations. [26,52]
Vitamin E and N-acetylcysteine (NAC) are reported to considerably improve lifespan in the genetic-based mitochondrial complex I disease C. elegans model, and to significantly protect against brain death in zebra fish exposed to a toxin with mitochondrial electron transport chain complexes (ETC) complex I inhibition [151], suggesting that vitamin E may potentially have a protective function in mitochondrial disease
Summary
Mitochondria possess their own replicating genetic system, and each one contains 100 to 10,000 copies of mitochondrial DNA (mtDNA) according to cell type and developmental stage [1]. Clinical manifestations of mitochondrial disorders (MD) may be due to mtDNA mutations, including point mutations or complex rearrangements of mtDNA as well as nuclear mutations, leading to mitochondrial DNA depletion or deletions [15]. Clinical manifestations of mitochondrial disorders may be present if the percentage of mutated mtDNA in a cell or tissue surpasses the threshold each tissue has (threshold effect) [16,17]. 2. Clinical Manifestations of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes (MELAS) Syndrome. The missense mutation maps to a conserved residue in the MT-TL1 gene coding for tRNA-leu(UUR), which is presumably used to impair the synthesis of mitochondrial protein [51].Apart from MELAS syndrome, the phenotypes associated to the mtDNA A3243Gmutation are variable between patients, including neurological and nonneurological presentations which range from asymptomatic carriers to severe phenotypes; mtDNA A3243G accounts for approximately 80% of the causative mutations. Several other mtDNA mutations, such as T3271C, A 3252G, T3291C, G3959A, A10134C, T10191C, G10197A [55], G13513A [56], and T10158C [57] as well as mutations in nuclear genes such as the polymerase gamma 1 (POLG1) [58] and PDHC deficiency [59] can cause MELAS syndrome
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
