Naslov
BNIP3L/NIX regulacija u selektivnoj autofagiji mitohondrija
(BNIP3L/NIX regulation in selective autophagy of mitochondria)

Autori
Marinković, Mija ; Novak, Ivana

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

Skup
2nd annual symposium Woman in Autophagy

Mjesto i datum
New York City (NY), Sjedinjene Američke Države, 22.11.2021. - 23.11.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
BNIP3L/NIX ; mitofagija ; fosforilacija ; dimerizacija
(BNIP3L/NIX ; mitophagy ; phosphorylation ; dimerization)

Sažetak
Mitophagy, a form of autophagy specialized to selective removal of mitochondria, is crucial for elimination of dysfunctional mitochondria whose accumulation can lead to the development of neurodegenerative diseases and tumors. However, programmed mitophagy of healthy mitochondria is essential for differentiation of particular cell types, such as erythrocytes. BNIP3L/NIX receptor is shown to be important for the programmed removal of healthy mitochondria during terminal differentiation of erythrocytes but molecular mechanisms of selectivity are still very unclear. Here, we have investigated BNIP3L/NIX dimerization and phosphorylation as a potentially novel combined molecular mechanism underlying BNIP3L/NIX-dependent mitophagy. Phosphorylation of two serines, juxtaposed to BNIP3L/NIX LIR domain, provide the formation of new and stable interactions between the receptor and autophagosomal protein, also more robust recruitment of autophagosomes and efficient removal of mitochondria. Further, forming stable homodimers, BNIP3L/NIX recruits autophagosomes more robustly than its monomeric form. This dimerization is achieved by specific S212 dephosphorylation located in the intermembrane mitochondrial space and has the same effect on mitophagy initiation and progression as LIR phosphorylation. Finally, the combined mechanisms of LIR-dependent autophagosomal recruitment and receptor dimerization show a cumulative effect on BNIP3L/NIX receptor activation. Thus, the interplay between BNIP3L/NIX phosphorylation and dimerization indicates that the combined mechanism of LIR phosphorylation and receptor dimerization is needed for proper BNIP3L/NIX-dependent mitophagy initiation and progression. Lastly, this knowledge of the molecular basis of BNIP3L/NIX-dependent mitophagy regulation is crucial for better understanding the mechanisms of individual cell`s differentiation and the development of pathological conditions that underlie the disturbed process of mitophagy.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA