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Int. J. Mol. Sci. 2015, 16(9), 22509-22526; doi:10.3390/ijms160922509

Mitochondrial Optic Atrophy (OPA) 1 Processing Is Altered in Response to Neonatal Hypoxic-Ischemic Brain Injury

1
Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, St. Thomas' Hospital, SE1 7EH London, UK
2
Perinatal Center, Institute for Clinical Sciences and Physiology & Neuroscience, Sahlgrenska Academy, University of Gothenburg, 41685 Gothenburg, Sweden
3
Inserm, U 1141, 75019 Paris, France
4
University Paris Diderot, Sorbonne Paris Cité, UMRS 1141, 75019 Paris, France
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editors: Jaime M. Ross and Giuseppe Coppotelli
Received: 25 May 2015 / Revised: 26 August 2015 / Accepted: 11 September 2015 / Published: 17 September 2015
(This article belongs to the Special Issue Mitochondrial Dysfunction in Ageing and Diseases)
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Abstract

Perturbation of mitochondrial function and subsequent induction of cell death pathways are key hallmarks in neonatal hypoxic-ischemic (HI) injury, both in animal models and in term infants. Mitoprotective therapies therefore offer a new avenue for intervention for the babies who suffer life-long disabilities as a result of birth asphyxia. Here we show that after oxygen-glucose deprivation in primary neurons or in a mouse model of HI, mitochondrial protein homeostasis is altered, manifesting as a change in mitochondrial morphology and functional impairment. Furthermore we find that the mitochondrial fusion and cristae regulatory protein, OPA1, is aberrantly cleaved to shorter forms. OPA1 cleavage is normally regulated by a balanced action of the proteases Yme1L and Oma1. However, in primary neurons or after HI in vivo, protein expression of YmelL is also reduced, whereas no change is observed in Oma1 expression. Our data strongly suggest that alterations in mitochondria-shaping proteins are an early event in the pathogenesis of neonatal HI injury. View Full-Text
Keywords: mitochondria; OPA1; Oma1; Yme1L; oxygen-glucose deprivation (OGD); hypoxia-ischaemia; neonatal brain injury mitochondria; OPA1; Oma1; Yme1L; oxygen-glucose deprivation (OGD); hypoxia-ischaemia; neonatal brain injury
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Baburamani, A.A.; Hurling, C.; Stolp, H.; Sobotka, K.; Gressens, P.; Hagberg, H.; Thornton, C. Mitochondrial Optic Atrophy (OPA) 1 Processing Is Altered in Response to Neonatal Hypoxic-Ischemic Brain Injury. Int. J. Mol. Sci. 2015, 16, 22509-22526.

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