02548nas a2200325   4500000000100000008004100001260001200042653001400054653001700068653001200085653001700097653001000114100001500124700001200139700001700151700002300168700001200191700001500203700001200218700001500230700001400245700002500259700001700284245008900301856009100390300000800481490000700489520171200496022001402208       2024                            d  c03/202410aComplex I10aHeteroplasmy10aleprosy10aMitochondria10amtDNA1 ade Souza F1 aSilva C1 ade Araújo G1 aSantana-da-Silva M1 aGobbo A1 ada Silva M1 aPinto P1 ada Costa P1 aSalgado C1 aRibeiro-Dos-Santos A1 aCavalcante G00aMitochondrial variants of complex I genes associated with leprosy clinical subtypes.  uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944465/pdf/41598_2024_Article_57191.pdf  a1-80 v143 a<p>Leprosy is a chronic bacterial infection mainly caused by Mycobacterium leprae that primarily affects skin and peripheral nerves. Due to its ability to absorb carbon from the host cell, the bacillus became dependent on energy production, mainly through oxidative phosphorylation. In fact, variations in genes of Complex I of oxidative phosphorylation encoded by mtDNA have been associated with several diseases in humans, including bacterial infections, which are possible influencers in the host response to leprosy. Here, we investigated the presence of variants in the mtDNA genes encoding Complex I regarding leprosy, as well as the analysis of their pathogenicity in the studied cohort. We found an association of 74 mitochondrial variants with either of the polar forms, Pole T (Borderline Tuberculoid) or Pole L (Borderline Lepromatous and Lepromatous) of leprosy. Notably, six variants were exclusively found in both clinical poles of leprosy, including m.4158A&gt;G and m.4248T&gt;C in MT-ND1, m.13650C&gt;A, m.13674T&gt;C, m.12705C&gt;T and m.13263A&gt;G in MT-ND5, of which there are no previous reports in the global literature. Our observations reveal a substantial number of mutations among different groups of leprosy, highlighting a diverse range of consequences associated with mutations in genes across these groups. Furthermore, we suggest that the six specific variants exclusively identified in the case group could potentially play a crucial role in leprosy susceptibility and its clinical differentiation. These variants are believed to contribute to the instability and dysregulation of oxidative phosphorylation during the infection, further emphasizing their significance.</p>
  a2045-2322