A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
The ABL-MYC axis controls WIPI1-enhanced autophagy in lifespan extension
Tekijät: Sporbeck K, Haas ML, Pastor-Maldonado CJ, Schüssele DS, Hunter C, Takacs Z, Diogo de Oliveira AL, Franz-Wachtel M, Charsou C, Pfisterer SG, Gubas A, Haller PK, Knorr RL, Kaulich M, Macek B, Eskelinen EL, Simonsen A, Proikas-Cezanne T
Julkaisuvuosi: 2023
Journal: Communications Biology
Tietokannassa oleva lehden nimi: Communications biology
Lehden akronyymi: Commun Biol
Vuosikerta: 6
Numero: 1
ISSN: 2399-3642
eISSN: 2399-3642
DOI: https://doi.org/10.1038/s42003-023-05236-9
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/180548890
Human WIPI β-propellers function as PI3P effectors in autophagy, with WIPI4 and WIPI3 being able to link autophagy control by AMPK and TORC1 to the formation of autophagosomes. WIPI1, instead, assists WIPI2 in efficiently recruiting the ATG16L1 complex at the nascent autophagosome, which in turn promotes lipidation of LC3/GABARAP and autophagosome maturation. However, the specific role of WIPI1 and its regulation are unknown. Here, we discovered the ABL-ERK-MYC signalling axis controlling WIPI1. As a result of this signalling, MYC binds to the WIPI1 promoter and represses WIPI1 gene expression. When ABL-ERK-MYC signalling is counteracted, increased WIPI1 gene expression enhances the formation of autophagic membranes capable of migrating through tunnelling nanotubes to neighbouring cells with low autophagic activity. ABL-regulated WIPI1 function is relevant to lifespan control, as ABL deficiency in C. elegans increased gene expression of the WIPI1 orthologue ATG-18 and prolonged lifespan in a manner dependent on ATG-18. We propose that WIPI1 acts as an enhancer of autophagy that is physiologically relevant for regulating the level of autophagic activity over the lifespan.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
