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Nat Commun. 2018 Jun 7;9(1):2221. doi: 10.1038/s41467-018-04603-z.

Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints.

Author information

1
School of Medical Sciences, Griffith University, Southport, 4222, Qld, Australia. a.bezawork-geleta@griffith.edu.au.
2
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, University of Queensland, Brisbane, 4072, Qld, Australia. a.bezawork-geleta@griffith.edu.au.
3
Department of Biochemistry and Molecular Biology, Shenzhen University School of Medicine, Shenzhen, 518060, China.
4
College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul, 08826, Korea.
5
School of Medical Sciences, Griffith University, Southport, 4222, Qld, Australia.
6
Institute of Biotechnology, Czech Academy of Sciences, Prague-West, 25250, Czech Republic.
7
Institute of Molecular Genetics, Czech Academy of Sciences, Prague, 14220, Czech Republic.
8
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, 20892, MD, USA.
9
Faculty of Science, University of South Bohemia, Ceske Budejovice, 37005, Czech Republic.
10
Australian Proteome Analysis Facility, Macquarie University, North Ryde, 2109, NSW, Australia.
11
TATAA Biocenter, Gothenburg, 41103, Sweden.
12
Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, University of Queensland, Brisbane, 4072, Qld, Australia.
13
Malaghan Institute of Medical Research, Wellington, 6242, New Zealand.
14
Institute of Biotechnology, Czech Academy of Sciences, Prague-West, 25250, Czech Republic. jakub.rohlena@ibt.cas.cz.
15
College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul, 08826, Korea. psh@snu.ac.kr.
16
School of Medical Sciences, Griffith University, Southport, 4222, Qld, Australia. j.neuzil@griffith.edu.au.
17
Institute of Biotechnology, Czech Academy of Sciences, Prague-West, 25250, Czech Republic. j.neuzil@griffith.edu.au.

Abstract

Cell growth and survival depend on a delicate balance between energy production and synthesis of metabolites. Here, we provide evidence that an alternative mitochondrial complex II (CII) assembly, designated as CIIlow, serves as a checkpoint for metabolite biosynthesis under bioenergetic stress, with cells suppressing their energy utilization by modulating DNA synthesis and cell cycle progression. Depletion of CIIlow leads to an imbalance in energy utilization and metabolite synthesis, as evidenced by recovery of the de novo pyrimidine pathway and unlocking cell cycle arrest from the S-phase. In vitro experiments are further corroborated by analysis of paraganglioma tissues from patients with sporadic, SDHA and SDHB mutations. These findings suggest that CIIlow is a core complex inside mitochondria that provides homeostatic control of cellular metabolism depending on the availability of energy.

PMID:
29880867
PMCID:
PMC5992162
DOI:
10.1038/s41467-018-04603-z
[Indexed for MEDLINE]
Free PMC Article

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