Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin
Authors:Julia Ring1, Patrick Rockenfeller1, 3, Claudia Abraham1, Jelena Tadic1, Michael Poglitsch1, Katherina Schimmel1, 4, Julia Westermayer1, Simon Schauer1, Bettina Achleitner1, Christa Schimpel1, 5, Barbara Moitzi1, Gerald N. Rechberger1, 6, Stephan J. Sigrist7, 8, Didac Carmona-Gutierrez1, Guido Kroemer9, 10, 11, 12, 13, 14, 15, Sabrina Büttner1, 16, Tobias Eisenberg1, 2, Frank Madeo1, 2
doi: 10.15698/mic2017.12.603
Volume 4, pp. 411 to 422, published 30/11/2017.
1 Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria. 2 BioTechMed Graz, Graz, Austria. 3 Kent Fungal Group, School of Biosciences, University of Kent, Canterbury, UK. 4 Institute of Molecular and Translational Therapeutic Strategies (IMTTS), IFB-Tx, Hannover Medical School, Hannover, Germany. 5 BioNanoNet Forschungsgesellschaft mbH, Graz, Austria. 6 Omics Center Graz, BioTechMed-Graz, Graz, Austria. 7 Institute for Biology, Freie Universität Berlin, Berlin, Germany. 8 NeuroCure, Charité, Berlin, Germany. 9 Equipe 11 Labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. 10 Cell Biology and Metabolomics Platforms, Gustave Roussy Comprehensive Cancer Center, Villejuif, France. 11 INSERM, U1138, Paris, France. 12 Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 13 Université Pierre et Marie Curie, Paris, France. 14 Pôle de Biologie, Hôpital Européen Georges Pompidou, Paris, France. 15 Karolinska Institute, Department of Women’s and Children’s Health, Karolinska University Hospital Stockholm, Sweden. 16 Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Keywords:
SPG20, mitochondria, metabolism, respiration, pyruvate dehydrogenase, cell death, aging.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
Julia Ring, Patrick Rockenfeller, Claudia Abraham, Jelena Tadic, Michael Poglitsc, Katherina Schimmel, Julia Westermayer, Simon Schauer, Bettina Achleitner, Christa Schimpel, Barbara Moitzi, Gerald N. Rechberger, Stephan J. Sigrist, Didac Carmona-Gutierrez, Guido Kroemer, Sabrina Büttner, Tobias Eisenberg, Frank Madeo (2017). Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin. Microbial Cell 4(12): 411-422. doi: 10.15698/mic2017.12.603
© 2017 Ring et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Hereditary spastic paraplegias, a group of neurodegenerative disorders, can be caused by loss-of-function mutations in the protein spartin. However, the physiological role of spartin remains largely elusive. Here we show that heterologous expression of human or Drosophila spartin extends chronological lifespan of yeast, reducing age-associated ROS production, apoptosis, and necrosis. We demonstrate that spartin localizes to the proximity of mitochondria and physically interacts with proteins related to mitochondrial and respiratory metabolism. Interestingly, Nde1, the mitochondrial external NADH dehydrogenase, and Pda1, the core enzyme of the pyruvate dehydrogenase complex, are required for spartin-mediated cytoprotection. Furthermore, spartin interacts with the glycolysis enhancer phospo-fructo-kinase-2,6 (Pfk26) and is sufficient to complement for PFK26-deficiency at least in early aging. We conclude that mitochondria-related energy metabolism is crucial for spartin’s vital function during aging and uncover a network of specific interactors required for this function.