BNIP3L/NIX regulation in selective autophagy of mitochondria (CROSBI ID 716286)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Marinković, Mija ; Novak, Ivana
engleski
BNIP3L/NIX regulation in selective autophagy of mitochondria
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.
BNIP3L/NIX ; mitophagy ; phosphorylation ; dimerization
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Podaci o prilogu
50-50.
2021.
nije evidentirano
objavljeno
Podaci o matičnoj publikaciji
Podaci o skupu
2nd annual symposium Woman in Autophagy
poster
22.11.2021-23.11.2021
New York City (NY), Sjedinjene Američke Države