Loss of the mitochondrial i ‐AAA protease YME1L leads to ocular dysfunction and spinal axonopathy

Autor: Matteo Bergami, Timothy Wai, Esther Barth, Elena I. Rugarli, Sofia Ahola, Thomas Langer, Hans-Georg Sprenger, Tim König, Annika Hesseling, Thomas MacVicar, Gulzar Wani, Maria Patron
Přispěvatelé: Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], Dpt of Neuroscience and Brain Technologies [Genova], NeuroEngineering & bio-arTificial Synergic SystemS Laboratory [Genova] (NetS3 Lab), Istituto Italiano di Tecnologia (IIT)-Istituto Italiano di Tecnologia (IIT), Center for Biomolecular Magnetic Resonance, Goethe-Universität Frankfurt am Main-Institute for Organic Chemistry and Chemical Biology
Rok vydání: 2019
Předmět:
0301 basic medicine
Nervous system
Cerebellum
Medicine (General)
Mitochondrial Diseases
[SDV]Life Sciences [q-bio]
Degeneration (medical)
Mitochondrion
QH426-470
Eye
Microphthalmia
GTP Phosphohydrolases
Mice
0302 clinical medicine
Microphthalmos
News & Views
ComputingMilieux_MISCELLANEOUS
Research Articles
Neurons
Metalloendopeptidases
Cell biology
Mitochondria
medicine.anatomical_structure
Spinal Cord
Peripheral nervous system
mitochondrial proteostasis
Molecular Medicine
YME1L
axonal degeneration
Research Article
OMA1
Biology
Cataract
Mitochondrial Proteins
03 medical and health sciences
R5-920
Endopeptidases
medicine
Genetics
Animals
Gait Disorders
Neurologic
medicine.disease
Spinal cord
Disease Models
Animal
030104 developmental biology
Proteostasis
microphthalmia
ATPases Associated with Diverse Cellular Activities
Genetics
Gene Therapy & Genetic Disease
Nervous System Diseases
030217 neurology & neurosurgery
Neuroscience
Zdroj: EMBO Molecular Medicine
EMBO Mol Med
EMBO Molecular Medicine, Wiley Open Access, 2018, 11 (1), ⟨10.15252/emmm.201809288⟩
EMBO Molecular Medicine, Vol 11, Iss 1, Pp n/a-n/a (2019)
ISSN: 1757-4676
1757-4684
DOI: 10.15252/emmm.201809288
Popis: Mitochondria are organelles that are present in all nucleated cells in the body. They have manifold functions but famously generate ATP efficiently through the process of oxidative phosphorylation. This ensures all tissues have an adequate energy supply and underlines the need for a fully functional mitochondrial network. Since mitochondrial biogenesis and maintenance require components from two genetic sources, mitochondrial diseases can result from mutations in either the nuclear or the mitochondrial genome (mtDNA). Enigmatically, mitochondrial disease can affect individuals at any age and in any tissue (Lightowlers et al, 2015). For a subset of mutations, the genotype can be ascribed to a clinical phenotype and a number of mutations are associated with remarkable tissue selectivity (Boczonadi et al, 2018). However, the gene expression pathways governing this tissue‐specific presentation are far from clear. In this issue of EMBO Molecular Medicine, Sprenger et al (2019) use mouse models to investigate the consequences of deleting a mitochondrial protease, YME1L, in neuronal/glial precursors. The loss causes multiple defects at both cell and tissue level, including a marked fragmentation of the mitochondrial network. Tandem depletion of a second mitochondrial protease, Oma1, successfully restored the mitochondrial connectivity, but did not rescue the ocular defects and caused an earlier onset of neurological dysfunction. Thus, in addition to other findings, the authors conclude that a fragmented mitochondrial network contributes less to the disease phenotype than the disruption of mitochondrial proteostasis.
Databáze: OpenAIRE
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