Regulation of Bnip3L/Nix mitophagy receptor by phosphorylation and dimerization (CROSBI ID 652327)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa
Podaci o odgovornosti
Marinković, Mija ; Buljubašić, Maja ; Šprung, Matilda ; Rogov, Vladimir ; Hamacher-Brady, Anne ; Brady, Nathan ; Dotsch, Volker ; Dikic, Ivan ; Novak, Ivana
engleski
Regulation of Bnip3L/Nix mitophagy receptor by phosphorylation and dimerization
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.
autophagy, Nix protein, mitophagy, phosphorylation
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Podaci o prilogu
188-188.
2017.
objavljeno
Podaci o matičnoj publikaciji
Podaci o skupu
Autophagy - From molecular principles to humam diseases, EMBO
poster
25.09.2017-29.09.2017
Dubrovnik, Hrvatska