Naslov
Regulation of Bnip3L/Nix mitophagy receptor by phosphorylation and dimerization

Autori
Marinković, Mija ; Buljubašić, Maja ; Šprung, Matilda ; Rogov, Vladimir ; Hamacher-Brady, Anne ; Brady, Nathan ; Dotsch, Volker ; Dikic, Ivan ; Novak, Ivana

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Autophagy: From molecular principles to human diseases / Genau, Heide ; Stolz, Alexandra - Nürnberg, 2017, 188-188

Skup
Autophagy - From molecular principles to humam diseases, EMBO

Mjesto i datum
Dubrovnik, Hrvatska, 25.09.2017. - 29.09.2017

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
autophagy, Nix protein, mitophagy, phosphorylation

Sažetak
Recent studies in the field of neurodegenerative diseases, heart diseases and cancer reveal the importance of successful removal of accumulated and damaged mitochondria by mitophagy. This process is fine-tuned by mitophagy receptors that are responsible for the recognition between the selected mitochondria and autophagosomal membrane. Several mitophagy receptors have been discovered (Atg32, Bnip3, Bnip3L/Nix, Bcl2L13 and FUNDC1), each containing LC3- interacting region (LIR) responsible for the recognition of the Atg8/LC3/GABARAP proteins exposed at the surface of the autophagosomal membrane. In the focus of our research is Bnip3L/Nix receptor responsible for the mitochondrial removal during the terminal differentiation of erythrocytes. Currently, we are investigating two mechanisms of Bnip3L/Nix regulation, phosphorylation and dimerization. We have obtained cellular, biochemical and biophysical evidence that phosphorylation of Bnip3L/Nix receptor’s LIR domain enhances its interactions with Atg8/LC3/GABARAP family proteins. The trigger for LIR phosphorylation and activation of mitophagy is still unknown. Regarding dimerization, our preliminary results suggest that Bnip3L/Nix forms homodimers and recruits autophagosomes stronger than monomers. Moreover, we have detected several amino acid residues at the C-teminal part of the protein responsible for dimerization. Amino acid substitutions of the key residues lead to abolishment of the dimer formation resulting in the lower LC3-Bnip3L/Nix recognition and subsequently lower mitophagy induction. Our latest results on dimerization status of the receptor and its influences on mitophagy initiation and progression including the interplay between phosphorylation and dimerization will be discussed.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Temeljne medicinske znanosti

POVEZANOST RADA