Search Results (3)

Chronic social isolation (CSIS), a known risk factor for the development of major depressive disorders, is associated with hippocampal dysfunction. In rodent models, CSIS produces two phenotypes: CSIS-susceptible, which develop depressive- and anxiety-like behaviors, and CSIS-resilient, which maintain normal behavior despite stress. However, the biological mechanisms underlying resilience to stress remain elusive. Mitochondria, as central regulators of neuronal energy metabolism and redox balance, are potential mediators of stress susceptibility and resilience. This review summarizes comparative proteomic analyses of hippocampal nonsynaptic mitochondria (NSM) and synaptosome-enriched mitochondria from CSIS-susceptible and CSIS-resilient rats along with controls. In NSM of resilient rats relative to susceptible rats, remodeling enhanced energy production, limited reactive oxygen species, stabilized phosphate transport, and promoted removal of damaged components. Compared with controls, these changes optimized energy production, and selectively downregulated oxidative stress-promoting proteins. Conversely, synaptosome-enriched mitochondria from resilient rats showed downregulation of proteins related to synaptic energy metabolism and redox balance relative to CSIS-susceptible rats, but demonstrated upregulation of bioenergetic and antioxidant enzymes, molecular chaperones, and neuroprotective factors compared with controls. These proteomic signatures both highlight mitochondrial adaptability in promoting stress resilience and identify mitochondria as promising targets for the development of novel antidepressant therapies. Full article

Synapses are particularly susceptible to the effects of advancing age, and mitochondria have long been implicated as organelles contributing to this compartmental vulnerability. Despite this, the mitochondrial molecular cascades promoting age-dependent synaptic demise remain to be elucidated. Here, we sought to examine how the synaptic mitochondrial proteome (including strongly mitochondrial associated proteins) was dynamically and temporally regulated throughout ageing to determine whether alterations in the expression of individual candidates can influence synaptic stability/morphology. Proteomic profiling of wild-type mouse cortical synaptic and non-synaptic mitochondria across the lifespan revealed significant age-dependent heterogeneity between mitochondrial subpopulations, with aged organelles exhibiting unique protein expression profiles. Recapitulation of aged synaptic mitochondrial protein expression at the Drosophila neuromuscular junction has the propensity to perturb the synaptic architecture, demonstrating that temporal regulation of the mitochondrial proteome may directly modulate the stability of the synapse in vivo. Full article

The protein phosphorylation of the membrane-bound mitochondrial proteins has become of interest from the point of view of its regulatory role of the function of the respiratory chain, opening of the mitochondrial permeability transition pore (mPTP), and initiation of apoptosis. Earlier, we noticed that upon phosphorylation of proteins in some proteins, the degree of their phosphorylation increases with the opening of mPTP. Two isoforms of myelin basic protein and cyclic nucleotide phosphodiesterase were identified in rat brain non-synaptic mitochondria and it was concluded that they are involved in mPTP regulation. In the present study, using the mass spectrometry method, the phosphorylated protein was identified as Calpain 3 in rat brain non-synaptic mitochondria. In the present study, the phosphoprotein Calpain-3 (p94) (CAPN3) was identified in the rat brain mitochondria as a phosphorylated truncated form of p60–62 kDa by two-dimensional electrophoresis and mass spectrometry. We showed that the calpain inhibitor, calpeptin, was able to suppress the Ca²⁺ efflux from mitochondria, preventing the opening of mPTP. It was found that phosphorylated truncated CALP3 with a molecular weight of 60–62 contains p-Tyr, which indicates the possible involvement of protein tyrosine phosphatase in this process. Full article