Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Gross, AS; Zimmermann, A; Pendl, T; Schroeder, S; Schoenlechner, H; Knittelfelder, O; Lamplmayr, L; Santiso, A; Aufschnaiter, A; Waltenstorfer, D; Ortonobes Lara, S; Stryeck, S; Kast, C; Ruckenstuhl, C; Hofer, SJ; Michelitsch, B; Woelflingseder, M; Müller, R; Carmona-Gutierrez, D; Madl, T; Büttner, S; Fröhlich, KU; Shevchenko, A; Eisenberg, T.
Acetyl-CoA carboxylase 1-dependent lipogenesis promotes autophagy downstream of AMPK.
J Biol Chem. 2019; 294(32): 12020-12039. [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Madl Tobias
Michelitsch Birgit
Stryeck Sarah
Altmetrics:

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Number of Figures: 8
| | | | | | | |
Abstract:
Autophagy, a membrane-dependent catabolic process, ensures survival of aging cells and depends on the cellular energetic status. Acetyl-CoA carboxylase 1 (Acc1) connects central energy metabolism to lipid biosynthesis and is rate-limiting for the de novo synthesis of lipids. However, it is unclear how de novo lipogenesis and its metabolic consequences affect autophagic activity. Here, we show that in aging yeast, autophagy levels highly depend on the activity of Acc1. Constitutively active Acc1 (acc1S/A ) or a deletion of the Acc1 negative regulator, Snf1 (yeast AMPK), shows elevated autophagy levels, which can be reversed by the Acc1 inhibitor soraphen A. Vice versa, pharmacological inhibition of Acc1 drastically reduces cell survival and results in the accumulation of Atg8-positive structures at the vacuolar membrane, suggesting late defects in the autophagic cascade. As expected, acc1S/A cells exhibit a reduction in acetate/acetyl-CoA availability along with elevated cellular lipid content. However, concomitant administration of acetate fails to fully revert the increase in autophagy exerted by acc1S/A Instead, administration of oleate, while mimicking constitutively active Acc1 in WT cells, alleviates the vacuolar fusion defects induced by Acc1 inhibition. Our results argue for a largely lipid-dependent process of autophagy regulation downstream of Acc1. We present a versatile genetic model to investigate the complex relationship between acetate metabolism, lipid homeostasis, and autophagy and propose Acc1-dependent lipogenesis as a fundamental metabolic path downstream of Snf1 to maintain autophagy and survival during cellular aging. © 2019 Gross et al.

Find related publications in this database (Keywords)
acetyl coenzyme A (acetyl-CoA)
acetate
aging
autophagy
lipid metabolism
yeast
Acc1
acetyl-CoA carboxylase 1
AMPK
oleate
Snf1
lipogenesis
© Med Uni Graz Impressum