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| Status |
Public on Aug 28, 2019 |
| Title |
mTORC1 dependent lipid signalling drives acute proteolytic rewiring of mitochondria by YME1L |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Metabolic reprogramming of mitochondria occurs during development, cell differentiation and in disease and is coupled to changes in mitochondrial mass and shape. Here, we demonstrate that the i-AAA protease YME1L rewires the proteome of pre-existing mitochondria in response to hypoxia or nutrient starvation. Inhibition of mTORC1 induces a lipid signalling cascade via the phosphatidic acid phosphatase LIPIN1, which decreases phosphatidylethanolamine levels in mitochondrial membranes and promotes proteolysis. YME1L degrades mitochondrial protein translocases, lipid transfer proteins and metabolic enzymes to acutely limit mitochondrial biogenesis and support cell growth. YME1L-mediated mitochondrial reshaping ensures spheroid and xenograft growth of pancreatic ductal adenocarcinoma (PDAC) cells. Similar mitochondrial proteome changes occur in tumour tissues of PDAC patients, suggesting that YME1L is relevant to the pathophysiology of specific solid tumours. Our results identify the mTORC1-LIPIN1-YME1L axis as a novel post-translational regulator of mitochondrial proteostasis at the interface of metabolism and mitochondrial dynamics.
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| Overall design |
Transcript profiles of WT mouse embryonic fibroblasts (MEF) incubated in normoxia (21% O2) or hypoxia (0.5 % O2) for 16 h. The dataset includes biological triplicates for each condition (6 samples in total)
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| Contributor(s) |
MacVicar T, Langer T, Altmüller J, Metge F |
| Citation(s) |
31695197 |
| |
| Submission date |
Jul 03, 2019 |
| Last update date |
May 03, 2022 |
| Contact name |
Thomas MacVicar |
| E-mail(s) |
[email protected]
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| Organization name |
Max Planck Institute for Biology of Ageing
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| Street address |
Joseph-Stelzmann Str 9B
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| City |
Cologne |
| ZIP/Postal code |
50931 |
| Country |
Germany |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA552462 |
| SRA |
SRP212864 |
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