Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin
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 chronologic...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Shared Science Publishers OG
2017-11-01
|
| Series: | Microbial Cell |
| Subjects: | |
| Online Access: | http://microbialcell.com/researcharticles/mitochondrial-energy-metabolism-is-required-for-lifespan-extension-by-the-spastic-paraplegia-associated-protein-spartin/ |
| _version_ | 1819299122530746368 |
|---|---|
| author | Julia Ring Patrick Rockenfeller Claudia Abraham Jelena Tadic Michael Poglitsch 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 |
| author_facet | Julia Ring Patrick Rockenfeller Claudia Abraham Jelena Tadic Michael Poglitsch 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 |
| author_sort | Julia Ring |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-24T05:40:46Z |
| format | Article |
| id | doaj.art-345f31f335df4374b65be0f350fe5c1c |
| institution | Directory Open Access Journal |
| issn | 2311-2638 |
| language | English |
| last_indexed | 2024-12-24T05:40:46Z |
| publishDate | 2017-11-01 |
| publisher | Shared Science Publishers OG |
| record_format | Article |
| series | Microbial Cell |
| spelling | doaj.art-345f31f335df4374b65be0f350fe5c1c2022-12-21T17:12:49ZengShared Science Publishers OGMicrobial Cell2311-26382017-11-0141241142210.15698/mic2017.12.603Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartinJulia Ring0Patrick Rockenfeller1Claudia Abraham2Jelena Tadic3Michael Poglitsch4Katherina Schimmel5Julia Westermayer6Simon Schauer7Bettina Achleitner8Christa Schimpel9Barbara Moitzi10Gerald N. Rechberger11Stephan J. Sigrist12Didac Carmona-Gutierrez13Guido Kroemer14Sabrina Büttner15Tobias Eisenberg16Frank Madeo17Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.Institute for Biology, Freie Universität Berlin, Berlin, Germany.Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.Equipe 11 Labellisée Ligue Contre le Cancer, Centre de Recherche des Cordeliers, Paris, France. Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.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.http://microbialcell.com/researcharticles/mitochondrial-energy-metabolism-is-required-for-lifespan-extension-by-the-spastic-paraplegia-associated-protein-spartin/SPG20mitochondriametabolismrespirationpyruvate dehydrogenasecell deathaging |
| spellingShingle | Julia Ring Patrick Rockenfeller Claudia Abraham Jelena Tadic Michael Poglitsch 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 Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin Microbial Cell SPG20 mitochondria metabolism respiration pyruvate dehydrogenase cell death aging |
| title | Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin |
| title_full | Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin |
| title_fullStr | Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin |
| title_full_unstemmed | Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin |
| title_short | Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin |
| title_sort | mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia associated protein spartin |
| topic | SPG20 mitochondria metabolism respiration pyruvate dehydrogenase cell death aging |
| url | http://microbialcell.com/researcharticles/mitochondrial-energy-metabolism-is-required-for-lifespan-extension-by-the-spastic-paraplegia-associated-protein-spartin/ |
| work_keys_str_mv | AT juliaring mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT patrickrockenfeller mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT claudiaabraham mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT jelenatadic mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT michaelpoglitsch mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT katherinaschimmel mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT juliawestermayer mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT simonschauer mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT bettinaachleitner mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT christaschimpel mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT barbaramoitzi mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT geraldnrechberger mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT stephanjsigrist mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT didaccarmonagutierrez mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT guidokroemer mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT sabrinabuttner mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT tobiaseisenberg mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin AT frankmadeo mitochondrialenergymetabolismisrequiredforlifespanextensionbythespasticparaplegiaassociatedproteinspartin |