A conserved MTMR lipid phosphatase increasingly suppresses autophagy in brain neurons during aging

Ageing is driven by the progressive, lifelong accumulation of cellular damage. Autophagy (cellular self-eating) functions as a major cell clearance mechanism to degrade such damages, and its capacity declines with age. Despite its physiological and medical significance, it remains largely unknown wh...

Teljes leírás

Elmentve itt :
Bibliográfiai részletek
Szerzők: Kovács Tibor
Szinyákovics Janka
Billes Viktor András
Murányi Gábor
Varga Virginia Beatrix
Bjelik Annamária
Légrádi Ádám
Szabó Melinda
Sándor Sára Anna
Kubinyi Enikő
Szekeres-Paraczky Cecília Kata
Szocsics Péter
Lőke János
Mulder Jun
Gulyás Balázs
Dobolyiné Renner Éva
Palkovits Miklós
Gulya Károly
Maglóczky Zsófia
Vellai Tibor
Dokumentumtípus: Cikk
Megjelent: 2022
Sorozat:SCIENTIFIC REPORTS 12 No. 1
Tárgyszavak:
doi:10.1038/s41598-022-24843-w

mtmt:33364095
Online Access:http://publicatio.bibl.u-szeged.hu/26415
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520 3 |a Ageing is driven by the progressive, lifelong accumulation of cellular damage. Autophagy (cellular self-eating) functions as a major cell clearance mechanism to degrade such damages, and its capacity declines with age. Despite its physiological and medical significance, it remains largely unknown why autophagy becomes incapable of effectively eliminating harmful cellular materials in many cells at advanced ages. Here we show that age-associated defects in autophagic degradation occur at both the early and late stages of the process. Furthermore, in the fruit fly Drosophila melanogaster , the myotubularin-related (MTMR) lipid phosphatase egg-derived tyrosine phosphatase (EDTP) known as an autophagy repressor gradually accumulates in brain neurons during the adult lifespan. The age-related increase in EDTP activity is associated with a growing DNA N 6 -adenine methylation at EDTP locus. MTMR14, the human counterpart of EDTP, also tends to accumulate with age in brain neurons. Thus, EDTP, and presumably MTMR14, promotes brain ageing by increasingly suppressing autophagy throughout adulthood. We propose that EDTP and MTMR14 phosphatases operate as endogenous pro-ageing factors setting the rate at which neurons age largely independently of environmental factors, and that autophagy is influenced by DNA N 6 -methyladenine levels in insects. 
650 4 |a Biológiai tudományok 
700 0 1 |a Szinyákovics Janka  |e aut 
700 0 1 |a Billes Viktor András  |e aut 
700 0 1 |a Murányi Gábor  |e aut 
700 0 1 |a Varga Virginia Beatrix  |e aut 
700 0 1 |a Bjelik Annamária  |e aut 
700 0 1 |a Légrádi Ádám  |e aut 
700 0 1 |a Szabó Melinda  |e aut 
700 0 1 |a Sándor Sára Anna  |e aut 
700 0 1 |a Kubinyi Enikő  |e aut 
700 0 2 |a Szekeres-Paraczky Cecília Kata  |e aut 
700 0 2 |a Szocsics Péter  |e aut 
700 0 2 |a Lőke János  |e aut 
700 0 2 |a Mulder Jun  |e aut 
700 0 2 |a Gulyás Balázs  |e aut 
700 0 2 |a Dobolyiné Renner Éva  |e aut 
700 0 2 |a Palkovits Miklós  |e aut 
700 0 2 |a Gulya Károly  |e aut 
700 0 2 |a Maglóczky Zsófia  |e aut 
700 0 2 |a Vellai Tibor  |e aut 
856 4 0 |u http://publicatio.bibl.u-szeged.hu/26415/2/srep12218172022.pdf  |z Dokumentum-elérés  
856 4 0 |u http://publicatio.bibl.u-szeged.hu/26415/1/srep12218172022-s1.pdf  |z Dokumentum-elérés