Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Direkt zur Navigaton springen.
Direkt zum Inhalt springen.

Navigation/Suche

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Ring, J; Rockenfeller, P; Abraham, C; Tadic, J; Poglitsch, M; Schimmel, K; Westermayer, J; Schauer, S; Achleitner, B; Schimpel, C; Moitzi, B; Rechberger, GN; Sigrist, SJ; Carmona-Gutierrez, D; Kroemer, G; Büttner, S; Eisenberg, T; Madeo, F.
Mitochondrial energy metabolism is required for lifespan extension by the spastic paraplegia-associated protein spartin.
Microb Cell. 2017; 4(12):411-422 Doi: 10.15698/mic2017.12.603 [OPEN ACCESS]
Web of Science PubMed FullText FullText_MUG

Co-Autor*innen der Med Uni Graz: Eisenberg Tobias; Rockenfeller Patrick; Schimpel Christa; Tadic Jelena
Altmetrics:
Dimensions Citations:
Plum Analytics:
Scite (citation analytics):
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.
Find related publications in this database (Keywords): SPG20; mitochondria; metabolism; respiration; pyruvate dehydrogenase; cell death; aging