bims-curels Biomed News
on Leigh syndrome
Issue of 2024‒06‒02
two papers selected by
Cure Mito Foundation



  1. Biochem J. 2024 Jun 05. 481(11): 683-715
      Human mitochondria possess a multi-copy circular genome, mitochondrial DNA (mtDNA), that is essential for cellular energy metabolism. The number of copies of mtDNA per cell, and their integrity, are maintained by nuclear-encoded mtDNA replication and repair machineries. Aberrant mtDNA replication and mtDNA breakage are believed to cause deletions within mtDNA. The genomic location and breakpoint sequences of these deletions show similar patterns across various inherited and acquired diseases, and are also observed during normal ageing, suggesting a common mechanism of deletion formation. However, an ongoing debate over the mechanism by which mtDNA replicates has made it difficult to develop clear and testable models for how mtDNA rearrangements arise and propagate at a molecular and cellular level. These deletions may impair energy metabolism if present in a high proportion of the mtDNA copies within the cell, and can be seen in primary mitochondrial diseases, either in sporadic cases or caused by autosomal variants in nuclear-encoded mtDNA maintenance genes. These mitochondrial diseases have diverse genetic causes and multiple modes of inheritance, and show notoriously broad clinical heterogeneity with complex tissue specificities, which further makes establishing genotype-phenotype relationships challenging. In this review, we aim to cover our current understanding of how the human mitochondrial genome is replicated, the mechanisms by which mtDNA replication and repair can lead to mtDNA instability in the form of large-scale rearrangements, how rearranged mtDNAs subsequently accumulate within cells, and the pathological consequences when this occurs.
    Keywords:  DNA damage; DNA replication and recombination; mitochondrial dysfunction; mtDNA
    DOI:  https://doi.org/10.1042/BCJ20230262
  2. Trends Endocrinol Metab. 2024 May 27. pii: S1043-2760(24)00119-X. [Epub ahead of print]
      Mitochondrial genetic defects caused by whole-body mutations typically affect different tissues in different ways. Elucidating the molecular determinants that cause certain cell types to be primarily affected has become a critical research target within the field. We propose a differential activation of the integrated stress response as a potential contributor to this tissue specificity.
    DOI:  https://doi.org/10.1016/j.tem.2024.05.001