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| Status |
Public on Jan 07, 2022 |
| Title |
Mitochondrial respiration maintains autophagy to support stress resistance in quiescent cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Mitochondrial oxidative phosphorylation (OXPHOS) generates ATP and is required for pyrimidine nucleotide synthesis during proliferation. In contrast, the role of OXPHOS in post-mitotic cells, beyond its contribution to ATP production, is less understood. Here, we show that in non-proliferating cells, OXPHOS ensures protection against oxidative stress by sustaining autophagy. Autophagy is suppressed and oxidative stress resistance is compromised in OXPHOS-deficient non-proliferating cells in vitro and in TFAM knockout mice in vivo, while attenuation of autophagy in OXPHOS-functional cells phenocopies the effects of OXPHOS deficiency. Mechanistically, the regulation of the autophagy / stress response by OXPHOS does not require changes in gene expression, AMPK/mTOR1/ULK1 signaling or NADH levels. Instead, OXPHOS maintains ROS levels to prevent activation of ATG4, a ROS-activated inhibitor of autophagy. We propose that protection against oxidative stress via the ROS-ATG4 axis is a novel function of mitochondrial respiration in non-proliferating cells that may have consequences for cancer therapy and beyond.
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| Overall design |
Cultured Ea.hy926 cells, parental (Eahy) and OXPHOS-deficient (Rho0), were grown to confluence and 4 biological replicates were collected for bulk RNA-seq analysis.
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| Contributor(s) |
Novais SM, Abaffy P, Khan S, Rohlena J |
| Citation(s) |
35258392 |
| |
| Submission date |
Feb 27, 2020 |
| Last update date |
Apr 08, 2022 |
| Contact name |
Jakub Rohlena |
| Organization name |
Institute of Biotechnology, CAS, v.v.i.
|
| Lab |
LABORATORY OF MOLECULAR THERAPY
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| Street address |
Prumyslova 595
|
| City |
Vestec by Prague |
| ZIP/Postal code |
25250 |
| Country |
Czech Republic |
| |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA609070 |
| SRA |
SRP250932 |
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