Dataset Information

Proteomics profiling of Neuronal Mitochondria

ABSTRACT: Mitochondria are the ‘power-houses’ of all cells, generating ATP to fuel numerous pathways which are vital for cellular form and function (1). Neuronal processes and synapses present a constant demand for ATP to maintain ionic gradients and neurotransmission events (2), promoting sub-populations of mitochondria to be enriched pre- and post-synaptically (3, 4). These mitochondria display unique enzymatic (5), calcium buffering (6, 7) and antioxidant properties (8) and have thus been associated in the pathogenesis of a variety of neurodegenerative diseases where the synapse is the primary target. In this study, we employed label-free proteomics to characterize the proteomes of synaptic and non-synaptic mitochondria following biochemical isolation (5). Discrete proteomic profiles exist between the two subpopulations of mitochondria and a molecular fingerprint of these differences is seemingly conserved between mammalian species. The majority of the constituents of this grouping have been previously associated with diseases of the nervous system. In addition, bioinformatic analysis of this conserved expression pattern indicated that differences in the properties of protein complex I may represent an important specialisation of synaptic mitochondria. Following this, in vivo assays of mitochondrial candidates using Drosophila larval fillet preparations were performed. Our data demonstrates that selective knock-down of intrinsic mitochondrial proteins alter synaptic morphology which may contribute to pathological processes during ageing and disease.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Brain, Neuron

SUBMITTER: Douglas Lamont

LAB HEAD: Tom Wishart

PROVIDER: PXD005537 | Pride | 2018-10-26

REPOSITORIES: Pride

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Publications

Proteomic profiling of neuronal mitochondria reveals modulators of synaptic architecture.

Graham Laura C LC Eaton Samantha L SL Brunton Paula J PJ Atrih Abdelmadjid A Smith Colin C Lamont Douglas J DJ Gillingwater Thomas H TH Pennetta Giuseppa G Skehel Paul P Wishart Thomas M TM

Molecular neurodegeneration 20171027 1

<h4>Background</h4>Neurons are highly polarized cells consisting of three distinct functional domains: the cell body (and associated dendrites), the axon and the synapse. Previously, it was believed that the clinical phenotypes of neurodegenerative diseases were caused by the loss of entire neurons, however it has recently become apparent that these neuronal sub-compartments can degenerate independently, with synapses being particularly vulnerable to a broad range of stimuli. Whilst the properti ...[more]

PMID: 29078798

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Project description:Although disruption of mitochondrial function has been associated with energetic deregulation in cancer, the chronological changes in mitochondria during cancer development remain unclear. With the aim to assess the role of mitochondria throughout cancer development, we analyzed samples chronologically obtained from induced hepatocellular carcinoma (HCC) in rats. In our analyses, we integrated mitochondrial proteomic data, mitochondrial metabolomic data and nuclear genome transcriptomic data. We used pathway over-representation and weighted gene co-expression network analysis (WGCNA) to integrate expression profiles of genes, miRNAs, proteins and metabolite levels throughout HCC development. Our results show that mitochondria are dynamic organelles presenting specific modifications in different stages of HCC development. For carcinogenesis, a modified resistant hepatocyte model was used. Rats were initiated with diethylnitrosamine (DEN) (200 mg/kg of body weight) at day 0. Then, 2-acetylaminofluorene (AAF) was administered (20 mg/kg per dose) at days 7, 8 and 9, followed by 3/5 partial hepatectomy (PH) at day 10. Three control groups of non-treated animals were sacrificed by exsanguination on the first day and at 9 and 18 months after the beginning of the experiment. Treated animals were sacrificed at 1, 7, 11 and 16 days and at 1, 9 and 18 months. Their livers were excised, washed in physiological saline solution, frozen with liquid nitrogen in 2-methyl butane and stored at -80°C. Once selected and separately collected nodular, tumoral and its adjacent tissues, total RNA was isolated using TriPureIsolation Reagent (Roche) according to the manufacturer’s protocol. The microarray analysis was performed using GeneChip Rat Exon 1.0 ST Arrays. Four replicas for each condition and controls were analyzed. This created 11 pairwise contrasts for the differential expression analysis. We grouped all evaluated conditions in three categories: i) early stages, including samples obtained since day one until one month after treatment, these were compared against rats without treatment sacrificed the first day; ii) tumor, nodular and its adjacent tissues obtained from nine months rats were compared against rats without treatment of the same age; and iii) tumor and its adjacent tissues obtained from eighteen months rats were compared against rats without treatment of the same age.

Dataset Information

Proteomics profiling of Neuronal Mitochondria

Publications

Proteomic profiling of neuronal mitochondria reveals modulators of synaptic architecture.

Similar Datasets

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