Quantitative Proteomics of Presynaptic Mitochondria Reveal an Overexpression and Biological Relevance of Neuronal MitoNEET in Postnatal Brain Development.


Journal

Developmental neurobiology
ISSN: 1932-846X
Titre abrégé: Dev Neurobiol
Pays: United States
ID NLM: 101300215

Informations de publication

Date de publication:
04 2019
Historique:
received: 30 07 2018
revised: 02 03 2019
accepted: 25 04 2019
pubmed: 3 5 2019
medline: 11 2 2020
entrez: 4 5 2019
Statut: ppublish

Résumé

Although it has been recognized that energy metabolism and mitochondrial structure and functional activity in the immature brain differs from that of the adult, few studies have examined mitochondria specifically at the neuronal synapse during postnatal brain development. In this study, we examined the presynaptic mitochondrial proteome in mice at postnatal day 7 and 42, a period that involves the formation and maturation of synapses. Application of two independent quantitative proteomics approaches - SWATH-MS and super-SILAC - revealed a total of 40 proteins as significantly differentially expressed in the presynaptic mitochondria. In addition to elevated levels of proteins known to be involved in ATP metabolic processes, our results identified increased levels of mitoNEET (Cisd1), an iron-sulfur containing protein that regulates mitochondrial bioenergetics. We found that mitoNEET overexpression plays a cell-type specific role in ATP synthesis and in neuronal cells promotes ATP generation. The elevated ATP levels in SH-SY5Y neuroblastoma cells were associated with increased mitochondrial membrane potential and a fragmented mitochondrial network, further supporting a role for mitoNEET as a key regulator of mitochondrial function.

Identifiants

pubmed: 31050203
doi: 10.1002/dneu.22684
pmc: PMC6543812
mid: NIHMS1026625
doi:

Substances chimiques

Iron-Binding Proteins 0
Membrane Proteins 0
mitoNEET protein, mouse 0
Adenosine Triphosphate 8L70Q75FXE

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

370-386

Subventions

Organisme : NIMH NIH HHS
ID : P30 MH062261
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA043258
Pays : United States

Informations de copyright

© 2019 Wiley Periodicals, Inc.

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Auteurs

Kelly L Stauch (KL)

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, 68198.

Lance M Villeneuve (LM)

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, 68198.

Steven Totusek (S)

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, 68198.

Benjamin Lamberty (B)

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, 68198.

Pawel Ciborowski (P)

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, 68198.

Howard S Fox (HS)

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, 68198.

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Classifications MeSH