Novel Mouse Models to Study Mitochondrial Proteostasis in the Nervous System
Event details
| Date | 04.02.2019 |
| Hour | 10:30 › 11:30 |
| Speaker | Hans-Georg Sprenger, Max Planck Institute for Biology of Ageing, Dept. Mitochondrial Proteostasis, Cologne (D) |
| Location | |
| Category | Conferences - Seminars |
SEMINAR of the LAUSANNE INTEGRATIVE METABOLISM and NUTRITION ALLIANCE (LIMNA)
Abstract:
Disturbances in the morphology and function of mitochondria cause neurological diseases, which can affect the central and peripheral nervous system. The i-AAA protease YME1L ensures mitochondrial proteostasis and regulates mitochondrial dynamics by processing of the dynamin-like GTPase OPA1. Mutations in YME1L cause a multi-systemic mitochondriopathy associated with neurological dysfunction and mitochondrial fragmentation but pathogenic mechanisms remained enigmatic. Here, we report on striking cell-type specific defects in mice lacking YME1L in the nervous system. YME1L-deficient mice manifest ocular dysfunction with microphthalmia and cataracts and at later stages of life develop deficiencies in locomotor activity due to specific degeneration of spinal cord axons. We demonstrate that YME1L ensures efficient mitochondrial transport in neurons and maintains mitochondrial proteostasis and dynamics in vivo. Additional deletion of Oma1 restores tubular mitochondria but deteriorates axonal degeneration in the absence of YME1L, demonstrating that impaired mitochondrial proteostasis rather than mitochondrial fragmentation cause trafficking defects and the observed neurological dysfunction.
Abstract:
Disturbances in the morphology and function of mitochondria cause neurological diseases, which can affect the central and peripheral nervous system. The i-AAA protease YME1L ensures mitochondrial proteostasis and regulates mitochondrial dynamics by processing of the dynamin-like GTPase OPA1. Mutations in YME1L cause a multi-systemic mitochondriopathy associated with neurological dysfunction and mitochondrial fragmentation but pathogenic mechanisms remained enigmatic. Here, we report on striking cell-type specific defects in mice lacking YME1L in the nervous system. YME1L-deficient mice manifest ocular dysfunction with microphthalmia and cataracts and at later stages of life develop deficiencies in locomotor activity due to specific degeneration of spinal cord axons. We demonstrate that YME1L ensures efficient mitochondrial transport in neurons and maintains mitochondrial proteostasis and dynamics in vivo. Additional deletion of Oma1 restores tubular mitochondria but deteriorates axonal degeneration in the absence of YME1L, demonstrating that impaired mitochondrial proteostasis rather than mitochondrial fragmentation cause trafficking defects and the observed neurological dysfunction.
Practical information
- Informed public
- Free
Organizer
- Johan Auwerx on behalf of the Lausanne Integrative Metabolism and Nutrition Alliance - LIMNA
Contact
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