PhD Scientific Days 2023

Molecular Sciences - Posters L

Role of Autophagy in Maintaining the Integrity of the Mitochondrial and the Nuclear Genomes

Előadó neve

Niftullayev, First name

Neptun code

N/A

Előadó munkahelye

MPI for Biology of Ageing/ University of Cologne

Előadó telefonszáma

+4915226065639

Előadó e-mail címe

SNiftullayev@age.mpg.de

Az előadás címe

Role of Autophagy in Maintaining the Integrity of the Mitochondrial and the Nuclear Genomes

Szerző(k) neve és munkahelye

Sadig Niftullayev1
Martin Graef2
1- MPI for Biology of Ageing; University of Cologne
2- Department of Molecular Biology and Genetics, Cornell University

Bemutatás módja

Poszter

Szekció

Molecular Sciences - Posters L

Language of the presentation

English

Preferred session

Molecular Sciences

Összefoglaló szövege

Mitochondria are unique organelles, which contain their own genome (mitochondrial DNA (mtDNA)). Cells contain ten to thousand copies of mtDNA in proteins and DNA containing structures called nucleoids. Despite the crucial role of mitochondria, much remains elusive about mtDNA maintenance and replication. Autophagy is an evolutionarily conserved mechanism, which is activated upon various stresses including nutritional stress. It has been well documented that dysfunctional autophagy leads to aberrations in nuclear DNA integrity, however the mechanistic link between autophagy and DNA damage is still lacking. Previously, we have reported that, upon nitrogen starvation, yeast cells lacking autophagy cannot maintain their dNTP balance and degrade their mtDNA in a polymerase γ (POLG)-dependent fashion. Here, we show that, in parallel to the mtDNA degradation, autophagy-deficient cells also suffer from nuclear DNA damage, which can be abolished by blocking either the POLG-dependent mtDNA degradation or Porin1 (VDAC1 homologue)-dependent mtDNA escape. Moreover, we observe that deletion of certain DNA damage repair (DDR) components such as genes encoding the MRX complex or HR pathway proteins prevent both mtDNA degradation and consequent DNA damage in autophagy-deficient cells. Finally, we also show that, unlike their wt counterparts, autophagy-deficient cells cannot resolve nuclear DNA damage. Together, our findings suggest a model where inability of the autophagy-deficient cells to resolve DNA damage leads to accumulation of DNA damage, which is exacerbated by mtDNA degradation and its Porin1-dependent escape. The project is part of the The Collaborative Research Centre (CRC)/Sonderforschungsbereich (SFB) 1218, which is funded by the DFG (German Research Foundation).

University and Doctoral School

Other, please specify in the next box

Other university and doctoral school, not listed above

University of Cologne

Supervisor

Thomas Langer

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7512

Start

11:36

End

11:41

Authors (legacy)

Sadig Niftullayev1
Martin Graef2
1- MPI for Biology of Ageing; University of Cologne
2- Department of Molecular Biology and Genetics, Cornell University