Naslov
Regulation of receptor-mediated mitophagy

Autori
Marinković, Mija ; Šprung, Matilda ; Rogov, Vladimir ; Dötsch, Volker ; Đikić, Ivan ; Novak, Ivana

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

Skup
Conference Mitochondria in life, Death and disease (EMBO 2019)

Mjesto i datum
Herceg Novi, Crna Gora, 24.09.2019. - 28.09.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
autophagy, mitophagy, BNIP3L/NIX

Sažetak
Mitophagy is crucial for maintaining mitochondrial quality control and cellular homeostasis. Two steps are indispensable: induction of general autophagy and priming of selected mitochondria for autophagic recognition. Mitochondrial priming is mediated either by the PINK1-PARKIN pathway or specific mitophagy receptors like scAtg32, BNIP3, BCL2L13, FUNDC1, FKBP8, PHB2 and BNIP3L/NIX that interact with Atg8/LC3/GABARAP family proteins in LIR- dependent manner to recruit autophagic machinery to mitochondria. The focus of our research is mitophagy receptor BNIP3L/NIX that plays a critical role in terminal differentiation of erythrocytes when complete mitochondrial content from the cell has to be removed. Our results suggest that mitophagic function of BNIP3L/NIX receptor is regulated by two possible mechanisms: phosphorylation and dimerization. Cellular, biochemical and biophysical evidence showed that phosphorylation of LIR domain of BNIP3L/NIX receptor enhances its interactions with Atg8/LC3/GABARAP family proteins on the autophagosomal membrane and is essential for mitophagy induction. Regarding receptor dimerization, our preliminary results suggest that BNIP3L/NIX homodimers recruit autophagosomes stronger than BNIP3L/NIX monomers to damaged mitochondria. Moreover, we have identified amino acid residues in BNIP3L/NIX responsible for dimerization whose mutations lead to abolishment of the dimer formation resulting in the lower LC3/GABARAP:BNIP3L/NIX recognition and reduced mitophagy induction. We hypothesize that mitophagy could be achieved through the interplay between phosphorylation and dimerization and further analysis will contribute to better understanding the role of mitophagy receptors in various diseases.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA