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Mitochondrial Changes (mitochondrial + change)
Selected AbstractsRegulation of skeletal muscle mitochondrial function: genes to proteinsACTA PHYSIOLOGICA, Issue 4 2010I. R. Lanza Abstract The impact of ageing on mitochondrial function and the deterministic role of mitochondria on senescence continue to be topics of vigorous debate. Many studies report that skeletal muscle mitochondrial content and function are reduced with ageing and metabolic diseases associated with insulin resistance. However, an accumulating body of literature suggests that physical inactivity typical of ageing may be a more important determinant of mitochondrial function than chronological age, per se. Reports of age-related declines in mitochondrial function have spawned a vast body of literature devoted to understanding the underlying mechanisms. These mechanisms include decreased abundance of mtDNA, reduced mRNA levels, as well as decreased synthesis and expression of mitochondrial proteins, ultimately resulting in decreased function of the whole organelle. Effective therapies to prevent, reverse or delay the onset of the aforementioned mitochondrial changes, regardless of their inevitability or precise underlying causes, require an intimate understanding of the processes that regulate mitochondrial biogenesis, which necessitates the coordinated regulation of nuclear and mitochondrial genomes. Herein we review the current thinking on regulation of mitochondrial biogenesis by transcription factors and transcriptional co-activators and the role of hormones and exercise in initiating this process. We review how exercise may help preserve mitochondrial content and functionality across the lifespan, and how physical inactivity is emerging as a major determinant of many age-associated changes at the level of the mitochondrion. We also review evidence that some mitochondrial changes with ageing are independent of exercise or physical activity and appear to be inevitable consequences of old age. [source] ERK signaling leads to mitochondrial dysfunction in extracellular zinc-induced neurotoxicityJOURNAL OF NEUROCHEMISTRY, Issue 2 2010Kai He J. Neurochem. (2010) 114, 452,461. Abstract A zinc-induced signaling pathway leading to extracellular signal-regulated kinase 1/2 (ERK1/2) activation and subsequent neuronal death has been investigated. We find that an extracellular zinc application stimulates biphasic phosphorylation of ERK1/2 and p38 MAPK in rat cultured neurons. The activation of ERK1/2, but not p38, is responsible for zinc neurotoxicity as only U0126, a MEK inhibitor that blocks ERK1/2 phosphorylation, significantly protects cortical neurons from zinc exposure. Over-expression of a dominant negative Ras mutant blocks zinc-induced Elk1-dependent gene expression in neurons, indicating the involvement of Ras activation in the zinc pathway leading to ERK phosphorylation and Elk1 signaling. We also find that zinc treatment results in neuronal mitochondrial hyperpolarization. Importantly, both U0126 and bongkrekic acid, an inhibitor of the mitochondrial adenine nucleotide translocase, effectively reduce zinc-triggered mitochondrial changes. As bongkrekic acid also prevents zinc-triggered neuronal death but not ERK1/2 phosphorylation, activation of MAPK signaling precedes and is required for mitochondrial dysfunction and cell death. These results provide new insight on the mechanism of extracellular zinc-induced toxicity in which the regulation of mitochondrial function by the Ras/MEK/ERK pathway is closely associated with neuronal viability. [source] Mitochondrial alterations in Parkinson's disease: new cluesJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Miquel Vila Abstract Mitochondrial dysfunction has long been associated with Parkinson's disease (PD). In particular, complex I impairment and subsequent oxidative stress have been widely demonstrated in experimental models of PD and in post-mortem PD samples. A recent wave of new studies is providing novel clues to the potential involvement of mitochondria in PD. In particular, (i) mitochondria-dependent programmed cell death pathways have been shown to be critical to PD-related dopaminergic neurodegeneration, (ii) many disease-causing proteins associated with familial forms of PD have been demonstrated to interact either directly or indirectly with mitochondria, (iii) aging-related mitochondrial changes, such as alterations in mitochondrial DNA, are increasingly being associated with PD, and (iv) anomalies in mitochondrial dynamics and intra-neuronal distribution are emerging as critical participants in the pathogenesis of PD. These new findings are revitalizing the field and reinforcing the potential role of mitochondria in the pathogenesis of PD. Whether a primary or secondary event, or part of a multi-factorial pathogenic process, mitochondrial dysfunction remains at the forefront of PD research and holds the promise as a potential molecular target for the development of new therapeutic strategies for this devastating, currently incurable, disease. [source] BH4 peptide derived from Bcl-xL and Bax-inhibitor peptide suppresses apoptotic mitochondrial changes in heat stressed bovine oocytesMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 7 2009Paolete Soto Mitochondria play an important role in the integration and transmission of cell death signals mediated by the Bcl-2 family proteins. Experiments were conducted to determine whether the anti-apoptotic peptides BH4 domain of Bcl-xL (TAT-BH4) and Bax inhibitor peptide (BIP) suppresses heat stress (HS) injury in oocytes by reduction of apoptotic-like events. Cumulus,oocyte complexes (COCs) were matured at 39°C (control) or 41°C (HS) for 21 hr then placed in maturation medium containing 0 or 100 µM BIP in water and 0 or 1 µM TAT-BH4 in dimethyl sulfoxide (DMSO), or a combination of both peptides (BIP,+,BH4). Peptide effects on embryo development, DNA fragmentation, mitochondrial membrane potential (,,m), and mitochondrial DNA (mtDNA) copy number were measured. All groups were fertilized and cultured in vitro at 39°C for 8 days. Compared to control, HS-treated oocytes induced a decrease in embryo development (P,<,0.05), increase in proportion of TUNEL-positive chromatin in oocytes and blastocysts (P,<,0.05), and loss of oocyte ,,m (P,<,0.001). In the presence of BIP or BIP,+,BH4, development of HS-treated oocytes into blastocysts was increased (P,<,0.05). Conversely, COCs matured with TAT-BH4 at 41°C showed reduced embryonic development (P,<,0.05). Exposure of HS-treated to each or both peptides resulted in a reduction of TUNEL frequency in oocytes and blastocysts cells derived from these oocytes (P,<,0.05). The loss of ,,m in HS-treated oocytes was not restored by exposure to BIP,+,BH4 and there was no effect in mtDNA copy number. In conclusion, the present results show that HS-induced apoptosis in bovine oocytes involves Bax and BH4 domain-dependent pathways. Mol. Reprod. Dev. 76: 637,646, 2009. © 2008 Wiley-Liss, Inc. [source] | ||||||||||