Absolute quantification of matrix metabolites reveals the dynamics of mitochondrial metabolism
Open accessAbstract
Mitochondria house metabolic pathways that impact most aspects of cellular physiology. While metabolite profiling by mass spectrometry is widely applied at the whole-cell level, it is not routinely possible to measure the concentrations of small molecules in mammalian organelles. We describe a method for the rapid and specific isolation of mitochondria and use it in tandem with a database of predicted mitochondrial metabolites ("MITObolome") to measure the matrix concentrations of more than 100 metabolites across various states of respiratory chain (RC) function. Disruption of the RC reveals extensive compartmentalization of mitochondrial metabolism and signatures unique to the inhibition of each RC complex. Pyruvate enables the proliferation of RC-deficient cells but has surprisingly limited effects on matrix contents. Interestingly, despite failing to restore matrix NADH/NAD balance, pyruvate does increase aspartate, likely through the exchange of matrix glutamate for cytosolic aspartate. We demonstrate the value of mitochondrial metabolite profiling and describe a strategy applicable to other organelles.
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Recent advances in metabolite extraction from isolated mitochondria demonstrate that metabolic flux models can be built with increasing precision.
“Recent advances in metabolite extraction from isolated mitochondria demonstrate that metabolic flux models can be built with increasing precision (289).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [289]
Metabolic flexibility is likely best understood as a system of interacting components to manage energy resources and requirements in health and disease.
“Metabolic flexibility is likely best understood as a system of interacting components to manage energy resources and requirements in health and disease”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [289]
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- Authors
- Chen, W. W., Freinkman, E., Wang, T., Birsoy, K., & Sabatini, D. M.
- Affiliations
- Broad Institute (US)
- Whitehead Institute for Biomedical Research (US)
- Rockefeller University (US)
- Corresponding author
- Sabatini, David M.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 166
- Issue
- 5
- Pages
- 1324-1337.e11
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5030821
- OpenAlex
- W2517861725
- Cited by
- 500
- References
- 50
- Citations by year
- 2026: 52 · 2025: 52 · 2024: 73 · 2023: 52 · 2022: 56 · 2021: 59 · 2020: 46 · 2019: 37 · 2018: 38 · 2017: 29 · 2016: 6
- FWCI
- 19.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- PMC
- Funders
- NIH (R01CA103866, R01CA129105, R37AI047389, F30 AG046047, F31 CA189437, K22 CA193660)
- Department of Defense (W81XWH-15-1-0230, W81XWH-15-1-0337)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- mitochondrial metabolism, mitochondrial isolation, electron transport inhibition, pyruvate, aspartic acid
- MeSH terms
- Electron Transport, HeLa Cells, Humans, Mitochondria, Pyruvic Acid, Metabolic Networks and Pathways, Metabolome
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