NARILIS seminar | Dr. David PLA-MARTIN, University of Cologne, Germany

  • When Oct 08, 2021 from 12:45 PM to 01:45 PM (Europe/Brussels / UTC200)
  • Where UNamur, L12 auditorium
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Selective degradation of mtDNA through autophagy

Dr. David Pla-Martín, postdoc researcher at University of Cologne, Institute of Vegetative Physiology, Germany

Rudolf Wiesner's research group

Mitochondria, as a central hub for metabolism, are affected in a wide variety of human diseases but also during normal ageing, where mtDNA integrity is compromised. Although toxic substances can cause mitochondrial damage, the most prevalent reason is the accumulation of alterations in mtDNA due to replication errors. Mutations in genes encoding proteins involved in mtDNA replication and maintenance, like the helicase Twinkle, lead to mitochondrial diseases, with brain and skeletal muscle regularly affected. Autophagy, and specifically mitophagy, are well-established pathways for mitochondrial turnover. Loss of mitochondrial quality control mechanisms, either by specific mutations of key players or by reduced autophagy activity, strikingly correlates with the acquirement of mtDNA mutations. However, how human cells eliminate mutant mtDNA is still obscure. Here we show that the elimination of mtDNA mutated molecules is a process involving nucleoid distribution and piecemeal mitophagy. mtDNA instability induces mitochondrial membrane remodelling and recruitment of the retromer complex to the mitochondria, in a process dependent on autophagy. In agreement, stimulation of autophagy by rapamycin selectively removes mtDNA deletions that accumulated during muscle regeneration in vivo, but without affecting mtDNA copy number. With these results, we unveil a new complex mechanism specifically targeting and removing mutant mtDNA which occurs outside the mitochondrial network.

Invited by Prof. Thierry Arnould, UNamur, Laboratory of Cellular and Molecular Biology (URBC)

L12 auditorium