Mitophagy is the selective autophagy of mitochondria and plays a critical role in mitochondrial health, cell viability, removal of sperm-derived mitochondria after fertilization and several neurological disorders. The canonical mitophagy pathway is driven by PINK1 accumulation upon mitochondrial depolarization, poly-ubiquitination via Parkin and recruitment of mitophagy-receptors to the mitochondrial surface. The isolation membrane/phagophore is formed around the marked organelle followed by enzymatic degradation in the autolysosome.
We investigate mitophagy induction and its downstream pathways using quantitative proteomics, CRISPR/Cas9 gene editing, fluorescent activated cell sorting and quantitative immunoblotting and microscopy. Our main goals are to understand how mitophagy activates upon mitochondrial protein misfolding and what are the functional links to the mitochondrial unfolded protein response.

N. Meyer, S. Zielke, J. B. Michaelis, B. Linder, V. Warnsmann, S. Rakel, H. D. Osiewacz, S. Fulda, M. Mittelbronn, C. Münch, C. Behrends, D. Kögel, AT 101 induces early mitochondrial dysfunction and HMOX1 (heme oxygenase 1) to trigger mitophagic cell death in glioma cells. Autophagy. 14, 1693–1709 (2018)

K. Yamano, C. Wang, S. A. Sarraf, C. Münch, R. Kikuchi, N. N. Noda, Y. Hizukuri, M. T. Kanemaki, W. Harper, K. Tanaka, N. Matsuda, R. J. Youle, Endosomal rab cycles regulate parkin-mediated mitophagy. Elife. 7 (2018)

D. Nguyen, S. Shaid, O. Vakhrusheva, S. E. Koschade, K. Klann, M. Thölken, F. Baker, J. Zhang, T. Oellerich, D. Sürün, A. Derlet, I. Haberbosch, S. Eimer, H. D. Osiewacz, C. Behrends,C. Münch, I. Dikic, C. H. Brandts, Loss of the selective autophagy receptor p62 impairs murine myeloid leukemia progression and mitophagy. Blood. 133, 168–179 (2019)