Defective post-transcriptional modification of tRNA disrupts mitochondrial homeostasis in Leber's hereditary optic neuropathy.

ABSTRACT: Leber's Hereditary Optic Neuropathy (LHON) is a rare, maternally inherited eye disease, predominantly due to the degeneration of retinal ganglion cells (RGCs). It is associated with a mitochondrial DNA (mtDNA) point mutation. Our previous study identified that the m.15927G > A homoplasmic mutation damaged the highly conserved base pairing (28C-42G) in anticodon stem of tRNA^Thr, caused deficient t⁶A modification and significantly decreased efficiency in aminoacylation and steady-state levels of tRNA^Thr, and led to mitochondrial dysfunction. Meanwhile, mechanisms underlying mtDNA mutations regulate intracellular signaling related to mitochondrial and cellular integrity are less explored. Here, we manifested that defective nucleotide modification induced by th

SUBMITTER: Zhang J 

PROVIDER: S-EPMC11421333 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature