Metabolomics. 2018;14(5):59. doi: 10.1007/s11306-018-1352-x. Epub 2018 Mar 31.
Metabolic profiling of isolated mitochondria and cytoplasm reveals compartment-specific metabolic responses.
Metabolomics : Official journal of the Metabolomic Society
Daqiang Pan, Caroline Lindau, Simon Lagies, Nils Wiedemann, Bernd Kammerer
Affiliations
Affiliations
- Center for Biological Systems Analysis, ZBSA, Albert-Ludwigs-University Freiburg, Habsburgerstraße 49, 79104, Freiburg, Germany.
- Institute of Pharmaceutical Sciences, Albert-Ludwigs-University Freiburg, 79104, Freiburg, Germany.
- Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert-Ludwigs-University Freiburg, Stefan-Meier-Str. 17, 79104, Freiburg, Germany.
- Faculty of Biology, University of Freiburg, 79104, Freiburg, Germany.
- Spemann Graduate School of Biology and Medicine (SGBM), Albert-Ludwigs-University Freiburg, 79104, Freiburg, Germany.
- Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, Albert-Ludwigs-University Freiburg, Stefan-Meier-Str. 17, 79104, Freiburg, Germany. [email protected].
- BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104, Freiburg, Germany. [email protected].
- Center for Biological Systems Analysis, ZBSA, Albert-Ludwigs-University Freiburg, Habsburgerstraße 49, 79104, Freiburg, Germany. [email protected].
- BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104, Freiburg, Germany. [email protected].
PMID: 29628813
PMCID: PMC5878833 DOI: 10.1007/s11306-018-1352-x
Abstract
INTRODUCTION: Subcellular compartmentalization enables eukaryotic cells to carry out different reactions at the same time, resulting in different metabolite pools in the subcellular compartments. Thus, mutations affecting the mitochondrial energy metabolism could cause different metabolic alterations in mitochondria compared to the cytoplasm. Given that the metabolite pool in the cytosol is larger than that of other subcellular compartments, metabolic profiling of total cells could miss these compartment-specific metabolic alterations.
OBJECTIVES: To reveal compartment-specific metabolic differences, mitochondria and the cytoplasmic fraction of baker's yeast
METHODS: Mitochondria were isolated through differential centrifugation and were analyzed together with the remaining cytoplasm by gas chromatography-mass spectrometry (GC-MS) based metabolic profiling.
RESULTS: Seventy-two metabolites were identified, of which eight were found exclusively in mitochondria and sixteen exclusively in the cytoplasm. Based on the metabolic signature of mitochondria and of the cytoplasm, mutants of the succinate dehydrogenase (respiratory chain complex II) and of the F
CONCLUSION: By applying metabolomics to isolated mitochondria and the corresponding cytoplasm, compartment-specific metabolic signatures can be identified. This subcellular metabolomics analysis is a powerful tool to study the molecular mechanism of compartment-specific metabolic homeostasis in response to mutations affecting the mitochondrial metabolism.
Keywords: ATP-synthase; Metabolic phenotyping; Metabolomics; Mitochondria; Succinate dehydrogenase; Yeast
Conflict of interest statement
Compliance with ethical standardsThe authors declare no conflict of interest.This article does not contain any studies with human participants or animals performed by any of the authors.
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