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A04 | Regulation and function of POLG-mediated mtDNA degradation

Martin Graef
Max Planck Institute for Biology of Ageing

Phone: +49 221 / 37970 470         
E-mail: Martin.Graef@uni-koeln.de

Running time within the CRC 1218: 07/2016 - 06/2024.


Autophagy is a highly conserved process required for cellular homeostasis during basal and stress conditions. Defects in autophagy result in the degradation of mitochondrial genomes (mtDNA) via a novel mechanism. The mitochondrial DNA polymerase gamma catalyzes not only the synthesis but also the degradation of mtDNA via its inherent 3’-5’ exonuclease activity. Within this project, we are examining the cellular mechanisms regulating the balance of the synthetic and degradative activities of POLG. In addition, we are characterizing the physiological consequences of POLG-mediated mtDNA degradation.

Project-related publications

Schütter, M. and Graef, M. (2020). Localized de novo phospholipid synthesis drives autophagosome biogenesis. Autophagy 1-2. doi: 10.1080/15548627.2020.1725379. [Epub ahead of print]

Schütter, M., Giavalisco, P., Brodesser, S., and Graef, M. (2020). Local fatty acid channeling into phospholipid synthesis drives phagophore expansion during autophagy. Cell 180, 135-149.e14.  [Epub ahead of print]

Gross, A. and Graef, M. (2019). Mechanisms of autophagy in metabolic stress response. J. Mol. Biol., pii: S0022-2836(19)30559-5. DOI: 10.1016/j.jmb.2019.09.005. [Epub ahead of print].

Cui, R., Medeiros, T.C., Willemsen, D., Iasi, L.N.M., Collier, G.E., Graef, M., Reichard, M., and Valenzano, D.R. (2019). Relaxed selection limits lifespan by increasing mutation load. Cell 178, 385-399.

Medeiros, T.C., Thomas, R.L., Ghillebert, R., and Graef, M. (2018). Autophagy balances mtDNA synthesis and degradation by DNA polymerase POLG during starvation. J. Cell Biol. 217, 1601-1611.

Medeiros, T.C., and Graef, M. (2018). Autophagy determines mtDNA copy number dynamics during starvation. Autophagy 15, 178-179.

Graef, M. (2018). Lipid droplet-mediated lipid and protein homeostasis in budding yeast. FEBS letters 592, 1291-1303.

Velázquez, A.P., Tatsuta, T., Ghillebert, R., Drescher, I., and Graef, M. (2016). Lipid droplet-mediated ER homeostasis regulates autophagy and cell survival during starvation. J. Cell Biol. 212, 621-631.

Velazquez, A.P., and Graef, M. (2016). Autophagy regulation depends on ER homeostasis controlled by lipid droplets. Autophagy 12, 1409-1410.