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Pregled bibliografske jedinice broj: 1034683

The role of mitochondrial protein BNIP3L/NIX phosphorylation and dimerization in mitophagy activation


Marinković, Mija; Buljubašić, Maja; Šprung, Matilda; Brady, Anne; Brady, Nathan; Dikic, Ivan; Novak, Ivana
The role of mitochondrial protein BNIP3L/NIX phosphorylation and dimerization in mitophagy activation // Spetses Summer School an EACR-FEBS advanced lecuture course „Molecular Mechanisms in Signal Transduction and Cancer“
Spetses, Grčka, 2017. str. 1-2 (poster, nije recenziran, sažetak, znanstveni)


CROSBI ID: 1034683 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
The role of mitochondrial protein BNIP3L/NIX phosphorylation and dimerization in mitophagy activation

Autori
Marinković, Mija ; Buljubašić, Maja ; Šprung, Matilda ; Brady, Anne ; Brady, Nathan ; Dikic, Ivan ; Novak, Ivana

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

Skup
Spetses Summer School an EACR-FEBS advanced lecuture course „Molecular Mechanisms in Signal Transduction and Cancer“

Mjesto i datum
Spetses, Grčka, 16–24.08.2017

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
Autophagy ; Nix protein ; mitophagy ; dimerization ; phosphorylation

Sažetak
Cellular homeostasis requires a proper balance between synthesis and degradation of cellular content. The two major degradative pathways in eukaryotic organisms are autophagy and the proteasome. Here, we will focus on autophagy, a conserved survival mechanism which acts as an adaptive response to environmental conditions such as starvation. With the discovery of the autophagy- related (ATG) genes in yeast many additional physiological processes have been linked to autophagy including maintenance of cellular and tissue homeostasis, aging, differentiation and development, innate and adaptive immunity. In addition to ATP production, mitochondria regulate calcium homeostasis, heme biosynthesis and cell survival/death decisions. Their dysfunction has been implicated in numerous conditions, including cancer, metabolic diseases, neurodegeneration, diabetes and aging. Mitophagy, the selective removal of damaged mitochondria through autophagy, is thus crucial for maintaining proper cellular functions. Indeed, mitophagy has been proposed to play critical roles in terminal differentiation of erythrocytes, paternal mitochondrial degradation, neurodegenerative diseases and cancer. Removal of damaged mitochondria through autophagy requires two steps: induction of general autophagy and priming of damaged mitochondria for selective autophagic recognition. Mitochondrial priming is mediated either by the Pink1-Parkin signaling pathway or the mitophagic receptors such as BNIP3, NIX/BNIP3L or FUNDC1. Discoveries of autophagic receptors that recognize specific cellular cargo have opened a new chapter in the autophagy field. Growing evidence of the function of particular autophagy receptors indicates that most of them are often working together in the same selective autophagy pathway, such as aggrephagy, xenophagy and mitophagy. In this part, we focused our research on receptors involved in mitophagy and their regulation. These receptors, such as scAtg32, BNIP3 and BNIP3L/NIX interact with Atg8/LC3/GABARAP family proteins in LIR-dependent manner and recruit autophagy machinery to damaged mitochondria. The lessons from xenophagy are directing future research towards better understanding of how mitophagy is activated and regulated. After all, this is not surprising because there is a well-accepted endosymbiotic theory that connects bacteria and mitochondria, where mitochondria are bacterial evolutionary descendants. Our results suggest that mitophagic function of NIX receptor is regulated by two possible mechanisms phosphorylation and homodimerisation. We showed cellular, biochemical and biophysical evidence that phosphorylation of LIR domain of NIX receptor enhances its interactions with Atg8/LC3/GABARAP family proteins on the autophagosomal membrane and is essential for mitophagy activation. Unfortunately we don`t know yet what is the trigger for LIR phosphorylation and activation of mitophagy. Another mechanism of NIX regulation is dimerisation via its transmembrane domain and we showed that Nix dimmers stronger recruite autophagosomes on damaged mitochondria. Understanding of mitophagy, and general autophagy regulation, is the major challenge for researchers of our time and their answers will help us to better understand the role of receptors and autophagy in disease development such as Parkinson`s disease and a number of other diseases.

Izvorni jezik
Hrvatski

Znanstvena područja
Biologija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekti:
HRZZ-UIP-2013-11-5246 - Uloga receptora autofagije u selektivnom uklanjanju mitohondrija (AutoMito) (Novak Nakir, Ivana, HRZZ - 2013-11) ( POIROT)

Ustanove:
Medicinski fakultet, Split

Profili:

Avatar Url Matilda Šprung (autor)

Avatar Url Maja Buljubašić (autor)

Avatar Url Ivana Novak (autor)


Citiraj ovu publikaciju

Marinković, Mija; Buljubašić, Maja; Šprung, Matilda; Brady, Anne; Brady, Nathan; Dikic, Ivan; Novak, Ivana
The role of mitochondrial protein BNIP3L/NIX phosphorylation and dimerization in mitophagy activation // Spetses Summer School an EACR-FEBS advanced lecuture course „Molecular Mechanisms in Signal Transduction and Cancer“
Spetses, Grčka, 2017. str. 1-2 (poster, nije recenziran, sažetak, znanstveni)
Marinković, M., Buljubašić, M., Šprung, M., Brady, A., Brady, N., Dikic, I. & Novak, I. (2017) The role of mitochondrial protein BNIP3L/NIX phosphorylation and dimerization in mitophagy activation. U: Spetses Summer School an EACR-FEBS advanced lecuture course „Molecular Mechanisms in Signal Transduction and Cancer“.
@article{article, year = {2017}, pages = {1-2}, keywords = {Autophagy, Nix protein, mitophagy, dimerization, phosphorylation}, title = {The role of mitochondrial protein BNIP3L/NIX phosphorylation and dimerization in mitophagy activation}, keyword = {Autophagy, Nix protein, mitophagy, dimerization, phosphorylation}, publisherplace = {Spetses, Gr\v{c}ka} }
@article{article, year = {2017}, pages = {1-2}, keywords = {Autophagy, Nix protein, mitophagy, dimerization, phosphorylation}, title = {The role of mitochondrial protein BNIP3L/NIX phosphorylation and dimerization in mitophagy activation}, keyword = {Autophagy, Nix protein, mitophagy, dimerization, phosphorylation}, publisherplace = {Spetses, Gr\v{c}ka} }




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