EMAIL THIS PAGE TO A FRIEND

Journal of proteomics

Synaptic mitochondria: a brain mitochondria cluster with a specific proteome.


PMID 25782751

Abstract

The synapse is a particularly important compartment of neurons. To reveal its molecular characteristics we isolated whole brain synaptic (sMito) and non-synaptic mitochondria (nsMito) from the mouse brain with purity validated by electron microscopy and fluorescence activated cell analysis and sorting. Two-dimensional differential gel electrophoresis and mass spectrometry based proteomics revealed 22 proteins with significantly higher and 34 proteins with significantly lower levels in sMito compared to nsMito. Expression differences in some oxidative stress related proteins, such as superoxide dismutase [Mn] (Sod2) and complement component 1Q subcomponent-binding protein (C1qbp), as well as some tricarboxylic acid cycle proteins, including isocitrate dehydrogenase subunit alpha (Idh3a) and ATP-forming β subunit of succinyl-CoA ligase (SuclA2), were verified by Western blot, the latter two also by immunohistochemistry. The data suggest altered tricarboxylic acid metabolism in energy supply of synapse while the marked differences in Sod2 and C1qbp support high sensitivity of synapses to oxidative stress. Further functional clustering demonstrated that proteins with higher synaptic levels are involved in synaptic transmission, lactate and glutathione metabolism. In contrast, mitochondrial proteins associated with glucose, lipid, ketone metabolism, signal transduction, morphogenesis, protein synthesis and transcription were enriched in nsMito. Altogether, the results suggest a specifically tuned composition of synaptic mitochondria. Neurons communicate with each other through synapse, a compartment metabolically isolated from the cell body. Mitochondria are concentrated in presynaptic terminals by active transport to provide energy supply for information transfer. Mitochondrial composition in the synapse may be different than in the cell body as some examples have demonstrated altered mitochondrial composition with cell type and cellular function in the muscle, heart and liver. Therefore, we posed the question whether protein composition of synaptic mitochondria reflects its specific functions. The determined protein difference pattern was in accordance with known functional specialties of high demand synaptic mitochondria. The data also suggest specifically tuned metabolic fluxes for energy production by means of interaction with glial cells surrounding the synapse. These findings provide possible mechanisms for dynamically adapting synaptic mitochondrial output to actual demand. In turn, an increased vulnerability of synaptic mitochondria to oxidative stress is implied by the data. This is important from theoretical but potentially also from therapeutic aspects. Mitochondria are known to be affected in some neurodegenerative and psychiatric disorders, and proteins with elevated level in synaptic mitochondria, e.g. C1qbp represent targets for future drug development, by which synaptic and non-synaptic mitochondria can be differentially affected.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB2501692
Anti-IDH3A (C-terminal) antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB1405983
Anti-IDH3A antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB2701643
Anti-idh3a antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB2701754
Anti-idh3a antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
AV42237
Anti-IDH3A antibody produced in rabbit, IgG fraction of antiserum
HPA041465
Anti-IDH3A antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
HPA039435
Anti-SUCLA2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2702040
Anti-SUCLA2 antibody produced in rabbit
SAB4200544
Anti-Synaptophysin antibody, Mouse monoclonal, clone SVP-38, purified from hybridoma cell culture
S9075
Anti-Synemin (N-terminal) antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
S8950
Anti-Synemin antibody produced in rabbit, ~1.5 mg/mL, affinity isolated antibody, buffered aqueous solution
SAB2102352
Anti-SYP antibody produced in rabbit, affinity isolated antibody
N8285
β-Nicotinamide adenine dinucleotide, pkg of 10 mg (per vial)
C21H27N7O14P2
N8410
β-Nicotinamide adenine dinucleotide, pkg of 20 mg (per vial)
C21H27N7O14P2
N8535
β-Nicotinamide adenine dinucleotide, pkg of 50 mg (per vial)
C21H27N7O14P2
N7004
β-Nicotinamide adenine dinucleotide hydrate, ≥96.5% (HPLC), ≥96.5% (spectrophotometric assay), from yeast
C21H27N7O14P2 · xH2O
N6522
β-Nicotinamide adenine dinucleotide hydrate, ≥98%, BioUltra, from yeast
C21H27N7O14P2 · xH2O
N1636
β-Nicotinamide adenine dinucleotide hydrate, purified by column chromatography, ≥99%
C21H27N7O14P2 · xH2O
N3014
β-Nicotinamide adenine dinucleotide hydrate, cell culture tested, ≥96.5% (HPLC), ≥96.5% (spectrophotometric assay), from yeast
C21H27N7O14P2 · xH2O
N7381
β-Nicotinamide adenine dinucleotide hydrate, Grade AA-1, ≥95% (HPLC)
C21H27N7O14P2 · xH2O
N1511
β-Nicotinamide adenine dinucleotide hydrate, ≥99%
C21H27N7O14P2 · xH2O
43410
β-Nicotinamide adenine dinucleotide hydrate, ≥95% (HPLC)
C21H27N7O14P2 · xH2O
N7132
β-Nicotinamide adenine dinucleotide lithium salt from Saccharomyces cerevisiae, ≥95%
C21H26LiN7O14P2
WH0023336M3 Monoclonal Anti-DMN antibody produced in mouse, clone 4G5, purified immunoglobulin, buffered aqueous solution
SAB1404966
Monoclonal Anti-DMN, (C-terminal) antibody produced in mouse, clone 4G5, ascites fluid
SAB4100035
Monoclonal Anti-IDH3A antibody produced in mouse, culture supernatant
WH0006855M1
Monoclonal Anti-SYP antibody produced in mouse, clone 3B3, purified immunoglobulin, buffered aqueous solution