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ATG12 Deficiency Leads to Tumor Cell Oncosis Owing to Diminished Mitochondrial Biogenesis and Reduced Cellular Bioenergetics

61 Pages Posted: 29 Jan 2019 Sneak Peek Status: Review Complete

See all articles by He Liu

He Liu

University of Bern - Institute of Pharmacology

Zhaoyue He

University of Bern - Institute of Pharmacology

Nina Germič

University of Bern - Institute of Pharmacology

Hyrijie Ademi

University of Bern - Institute of Pharmacology

Živa Frangež

University of Bern - Institute of Pharmacology

Andrea Felser

University of Bern - Institute of Clinical Chemistry

Jean-Marc Nuoffer

University of Bern - Institute of Clinical Chemistry

Cédric Bovet

University of Bern - Institute of Clinical Chemistry

Martin Grosek

University of Bern - Institute of Pharmacology

Irena Mlinarič- Raščan

University of Ljubljana - Faculty of Pharmacy

Bruno M. Humbel

University of Lausanne - Electron Microscopy Facility

Inti Zlobec

University of Bern - Institute of Pathology

Martin Fiedler

University of Bern - Institute of Clinical Chemistry

Aurel Perren

University of Bern - Institute of Pathology

Hans-Uwe Simon

University of Bern - Institute of Pharmacology

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Abstract

Liu et al. find a non-canonical role for an autophagy-related protein, ATG12, in regulating mitochondrial biogenesis and cellular bioenergetics. Cells deficient in ATG12 show distinct global metabolic features, decreasing β-oxidation (FAO), glycolysis, Krebs cycle (TCA cycle) activity, mitochondrial respiration and mitochondrial biogenesis as compared to control cells, leading in consequence to an insufficient energy supply and finally oncotic cell death, which does not occur in ATG12-deficient fibroblasts. ATG12, that we could detect partly at a mitochondrial localization, was upregulated in diverse types of solid tumors compared to the normal tissues in a multi-organ tissue microarray (TMA), thus suggesting a potential role for ATG12 in regulating cancer cell metabolism. Inducing oncosis by imposing an ATG12 deficiency in solid tumors might represent an anti-cancer therapy preferable to conventional caspase-dependent apoptosis that often shows undesirable consequences, such as incomplete cancer cell killing and silencing of the host immune system.

Suggested Citation

Liu, He and He, Zhaoyue and Germič, Nina and Ademi, Hyrijie and Frangež, Živa and Felser, Andrea and Nuoffer, Jean-Marc and Bovet, Cédric and Grosek, Martin and Mlinarič- Raščan, Irena and Humbel, Bruno M. and Zlobec, Inti and Fiedler, Martin and Perren, Aurel and Simon, Hans-Uwe, ATG12 Deficiency Leads to Tumor Cell Oncosis Owing to Diminished Mitochondrial Biogenesis and Reduced Cellular Bioenergetics (January 9, 2019). Available at SSRN: https://ssrn.com/abstract=3312729 or http://dx.doi.org/10.2139/ssrn.3312729
This is a paper under consideration at Cell Press and has not been peer-reviewed.

He Liu

University of Bern - Institute of Pharmacology

Gesellschaftsstrasse 49
Bern, 3001
Switzerland

Zhaoyue He

University of Bern - Institute of Pharmacology

Gesellschaftsstrasse 49
Bern, 3001
Switzerland

Nina Germič

University of Bern - Institute of Pharmacology

Gesellschaftsstrasse 49
Bern, 3001
Switzerland

Hyrijie Ademi

University of Bern - Institute of Pharmacology

Gesellschaftsstrasse 49
Bern, 3001
Switzerland

Živa Frangež

University of Bern - Institute of Pharmacology

Gesellschaftsstrasse 49
Bern, 3001
Switzerland

Andrea Felser

University of Bern - Institute of Clinical Chemistry

Gesellschaftsstrasse 49
Bern, 3001
Switzerland

Jean-Marc Nuoffer

University of Bern - Institute of Clinical Chemistry

Gesellschaftsstrasse 49
Bern, 3001
Switzerland

Cédric Bovet

University of Bern - Institute of Clinical Chemistry

Gesellschaftsstrasse 49
Bern, 3001
Switzerland

Martin Grosek

University of Bern - Institute of Pharmacology

Gesellschaftsstrasse 49
Bern, 3001
Switzerland

Irena Mlinarič- Raščan

University of Ljubljana - Faculty of Pharmacy

Aškerèeva
Slovenia

Bruno M. Humbel

University of Lausanne - Electron Microscopy Facility

Lausanne, Vaud CH-1015
Switzerland

Inti Zlobec

University of Bern - Institute of Pathology

Gesellschaftsstrasse 49
Bern, 3001
Switzerland

Martin Fiedler

University of Bern - Institute of Clinical Chemistry

Gesellschaftsstrasse 49
Bern, 3001
Switzerland

Aurel Perren

University of Bern - Institute of Pathology

Gesellschaftsstrasse 49
Bern, 3001
Switzerland

Hans-Uwe Simon (Contact Author)

University of Bern - Institute of Pharmacology ( email )

Gesellschaftsstrasse 49
Bern, 3001
Switzerland

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