Search results for "mitochondrion"
showing 10 items of 491 documents
Small molecule inhibitors of Apaf-1-related caspase- 3/-9 activation that control mitochondrial-dependent apoptosis
2006
10 pages, 5 figures.-- PMID: 16341125 [PubMed].-- Available online Dec 9, 2005.
Global gene expression profiles in skeletal muscle of monozygotic female twins discordant for hormone replacement therapy
2010
Summary Aging is accompanied by inexorable loss of muscle tissue. One of the underlying causes for this is the massive change in the hormonal milieu of the body. The role of a female sex steroid – estrogen – in these processes is frequently neglected, although the rapid decline in its production coincides with a steep deterioration in muscle performance. We recruited 54- to 62-year-old monozygotic female twin pairs discordant for postmenopausal hormone replacement therapy (HRT, n = 11 pairs; HRT use 7.3 ± 3.7 years) from the Finnish Twin Cohort to investigate the association of long-term, estrogen-based HRT with skeletal muscle transcriptome. Pathway analysis of muscle transcript profiles r…
Structural and Hereditary Chaperonopathies: Mutation
2013
This chapter deals with structural and hereditary chaperonopathies. The chaperonopathies caused by mutations in: sHsp, chaperonin genes (Hsp60 or Cpn60, and CCT subunits), Hsp40/DnaJ, Hsp70, sacsin, and dedicated chaperones (e.g., those involved in microtubule biogenesis, in maintenance of the respiratory chain inside the mitochondria, and others in various cell compartments and tissues), are described and discussed.
2015
The NG2 proteoglycan is characteristically expressed by oligodendrocyte progenitor cells (OPC) and also by aggressive brain tumours highly resistant to chemo- and radiation therapy. Oligodendrocyte-lineage cells are particularly sensitive to stress resulting in cell death in white matter after hypoxic or ischemic insults of premature infants and destruction of OPC in some types of Multiple Sclerosis lesions. Here we show that the NG2 proteoglycan binds OMI/HtrA2, a mitochondrial serine protease which is released from damaged mitochondria into the cytosol in response to stress. In the cytosol, OMI/HtrA2 initiates apoptosis by proteolytic degradation of anti-apoptotic factors. OPC in which NG…
Mitochondrial defects and neuromuscular degeneration caused by altered expression of Drosophila Gdap1: implications for the Charcot–Marie–Tooth neuro…
2014
One of the genes involved in Charcot-Marie-Tooth (CMT) disease, an inherited peripheral neuropathy, is GDAP1. In this work, we show that there is a true ortholog of this gene in Drosophila, which we have named Gdap1. By up- and down-regulation of Gdap1 in a tissue-specific manner, we show that altering its levels of expression produces changes in mitochondrial size, morphology and distribution, and neuronal and muscular degeneration. Interestingly, muscular degeneration is tissue-autonomous and not dependent on innervation. Metabolic analyses of our experimental genotypes suggest that alterations in oxidative stress are not a primary cause of the neuromuscular degeneration but a long-term c…
Junctophilin-1 is a modifier gene of GDAP1-related Charcot-Marie-Tooth disease.
2014
Mutations in the GDAP1 gene cause different forms of Charcot-Marie-Tooth (CMT) disease, and the primary clinical expression of this disease is markedly variable in the dominant inheritance form (CMT type 2K; CMT2K), in which carriers of the GDAP1 p.R120W mutation can display a wide range of clinical severity. We investigated the JPH1 gene as a genetic modifier of clinical expression variability because junctophilin-1 (JPH1) is a good positional and functional candidate. We demonstrated that the JPH1-GDAP1 cluster forms a paralogon and is conserved in vertebrates. Moreover, both proteins play a role in Ca(2+) homeostasis, and we demonstrated that JPH1 is able to restore the store-operated Ca…
The role of glia, mitochondria, and the immune system in glaucoma.
2009
Author(s): Tezel, Gulgun; Fourth ARVO/Pfizer Ophthalmics Research Institute Conference Working Group
Cell expression of GDAP1 in the nervous system and pathogenesis of Charcot-Marie-Tooth type 4A disease
2007
Abstract Mutations in the mitochondrial protein GDAP1 are the cause of Charcot-Marie-Tooth type 4A disease (CMT4A), a severe form of peripheral neuropathy associated with either demyelinating, axonal or intermediate pheno-types. GDAP1 is located in the outer mitochondrial membrane and it seems that may be related with the mitochondrial network dynamics. We are interested to define cell expression in the nervous system and the effect of mutations in mitochondrial morphology and pathogenesis of the disease. We investigated GDAP1 expression in the nervous system and dorsal root ganglia (DRG) neuron cultures. GDAP1 is expressed in motor and sensory neurons of the spinal cord and other large neu…
Hsp60 Friend and Foe of the Nervous System
2019
Hsp60 belongs to the subgroup of molecular chaperones named chaperonins and, typically, resides and functions in the mitochondria but it is also present in extramitochondrial sites. It chaperones client peptides as they fold to achieve the native conformation and also displays anti-stress roles by helping stress-damaged proteins regain a functional shape. Thus, Hsp60 is central to the integrity and functionality of mitochondria and energy production. All cells in the nervous system depend on Hsp60 so when the chaperonin malfunctions the consequences on nervous tissues are usually devastating, causing diverse diseases. These are the Hsp60 chaperonopathies, which can be genetic or acquired wi…
Mildronate and its neuroregulatory mechanisms: targeting the mitochondria, neuroinflammation, and protein expression.
2013
This review for the first time summarizes the data obtained in the neuropharmacological studies of mildronate, a drug previously known as a cardioprotective agent. In different animal models of neurotoxicity and neurodegenerative diseases, we demonstrated its neuroprotecting activity. By the use of immunohistochemical methods and Western blot analysis, as well as some selected behavioral tests, the new mechanisms of mildronate have been demonstrated: a regulatory effect on mitochondrial processes and on the expression of nerve cell proteins, which are involved in cell survival, functioning, and inflammation processes. Particular attention is paid to the capability of mildronate to stimulate…