Author
Listed:
- Thomas MacVicar
(Max-Planck-Institute for Biology of Ageing)
- Yohsuke Ohba
(Max-Planck-Institute for Biology of Ageing)
- Hendrik Nolte
(Max-Planck-Institute for Biology of Ageing
University of Cologne)
- Fiona Carola Mayer
(Max-Planck-Institute for Biology of Ageing)
- Takashi Tatsuta
(Max-Planck-Institute for Biology of Ageing)
- Hans-Georg Sprenger
(Max-Planck-Institute for Biology of Ageing
University of Cologne)
- Barbara Lindner
(University of Cologne)
- Yue Zhao
(University Hospital of Cologne)
- Jiahui Li
(University Hospital of Cologne)
- Christiane Bruns
(University Hospital of Cologne)
- Marcus Krüger
(University of Cologne
University of Cologne)
- Markus Habich
(University of Cologne)
- Jan Riemer
(University of Cologne)
- Robin Schwarzer
(University of Cologne)
- Manolis Pasparakis
(Max-Planck-Institute for Biology of Ageing
University of Cologne
University of Cologne)
- Sinika Henschke
(Max-Planck-Institute for Metabolism Research)
- Jens C. Brüning
(University of Cologne
Max-Planck-Institute for Metabolism Research
University Hospital of Cologne)
- Nicola Zamboni
(Molecular Systems Biology, ETH Zürich)
- Thomas Langer
(Max-Planck-Institute for Biology of Ageing
University of Cologne
University of Cologne)
Abstract
Reprogramming of mitochondria provides cells with the metabolic flexibility required to adapt to various developmental transitions such as stem cell activation or immune cell reprogramming, and to respond to environmental challenges such as those encountered under hypoxic conditions or during tumorigenesis1–3. Here we show 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 supports the growth of pancreatic ductal adenocarcinoma (PDAC) cells as spheroids or xenografts. Similar changes to the mitochondrial proteome occur in the tumour tissues of patients with PDAC, suggesting that YME1L is relevant to the pathophysiology of these tumours. Our results identify the mTORC1–LIPIN1–YME1L axis as a post-translational regulator of mitochondrial proteostasis at the interface between metabolism and mitochondrial dynamics.
Suggested Citation
Thomas MacVicar & Yohsuke Ohba & Hendrik Nolte & Fiona Carola Mayer & Takashi Tatsuta & Hans-Georg Sprenger & Barbara Lindner & Yue Zhao & Jiahui Li & Christiane Bruns & Marcus Krüger & Markus Habich , 2019.
"Lipid signalling drives proteolytic rewiring of mitochondria by YME1L,"
Nature, Nature, vol. 575(7782), pages 361-365, November.
Handle:
RePEc:nat:nature:v:575:y:2019:i:7782:d:10.1038_s41586-019-1738-6
DOI: 10.1038/s41586-019-1738-6
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Cited by:
- Claudio Bussi & Tiaan Heunis & Enrica Pellegrino & Elliott M. Bernard & Nourdine Bah & Mariana Silva Santos & Pierre Santucci & Beren Aylan & Angela Rodgers & Antony Fearns & Julia Mitschke & Christop, 2022.
"Lysosomal damage drives mitochondrial proteome remodelling and reprograms macrophage immunometabolism,"
Nature Communications, Nature, vol. 13(1), pages 1-22, December.
- Jiamin Qiu & Feng Yue & Peipei Zhu & Jingjuan Chen & Fan Xu & Lijia Zhang & Kun Ho Kim & Madigan M. Snyder & Nanjian Luo & Hao-wei Xu & Fang Huang & W. Andy Tao & Shihuan Kuang, 2023.
"FAM210A is essential for cold-induced mitochondrial remodeling in brown adipocytes,"
Nature Communications, Nature, vol. 14(1), pages 1-18, December.
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