P11, Tassula Proikas-Cezanne

Mitochondrial outer membrane as signaling hub in the control of autophagy

Mitochondria play an essential bioenergetic role, but also coordinate a large number of cellular functions such as metabolism, apoptosis and autophagy. Autophagy selectively targets compromised mitochondria for lysosomal degradation, a process known as mitophagy. Mitophagy receptors, such as optineurin (OPTN) recognize ubiquitinated mitochondrial outer membrane (MOM) proteins and associate with LC3 conjugated to the initial autophagosomal membranes (phagophores). Such phagophores elongate to sequester damaged mitochondria for lysosomal degradation. This process is compromised in neurodegeneration and leads to the harmful accumulation of damaged mitochondria.

WIPI proteins, a group of four beta-propellers in human (WIPI1 through WIPI4) that we identified earlier and that belong to an ancient family of proteins called PROPPIN, play important roles as PI3P effectors during autophagy initiation. In this context, WIPI1 and WIPI2 act upstream of LC3 and have been shown to be involved in Parkin-mediated mitophagy, marked by the involvement of the mitophagy receptor OPTN. Signaling events at the MOM that lead to the recruitment of WIPI1 and WIPI2, however, are poorly understood, especially in diseases with compromised mitophagy. In this project, we wish to contribute to uncovering such relevant molecular details, as more recent findings indicate that WIPI mutations contribute to the development of neurological abnormalities in humans.

Proikas-Cezanne group webpage

Proikas-Cezanne on Twitter: @TassulaPC

Maria von Linden Lecture

https://uni-tuebingen.de/fakultaeten/mathematisch-naturwissenschaftliche-fakultaet/fachbereiche/biologie/fachbereich/maria-von-linden-lecture/

GBM Studiengruppe Autophagie

http://autophagie-gbm.de/