41 research outputs found
Systems biology and bioenergetics: Structure–function relationships in feedback regulation of energy fluxes in vivo Mitochondrial interactosome
Lack of dystrophin is associated with altered integration of the mitochondria and ATPases in slow-twitch muscle cells of MDX mice
Braun U, Paju K, Eimre M, et al. Lack of dystrophin is associated with altered integration of the mitochondria and ATPases in slow-twitch muscle cells of MDX mice. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS. 2001;1505(2-3):258-270.The potential role of dystrophin-mediated control of systems integrating mitochondria with ATPases was assessed in muscle cells. Mitochondrial distribution and function in skinned cardiac and skeletal muscle fibers from dystrophin-deficient (MDX) and wild-type mice were compared. Laser confocal microscopy revealed disorganized mitochondrial arrays in m. gastrocnemius in MDX mice, whereas the other muscles appeared normal in this group. Irrespective of muscle type, the absence of dystrophin had no effect on the maximal capacity of oxidative phosphorylation, nor on coupling between oxidation and phosphorylation. However, in the myocardium and m. soleus, the coupling of mitochondrial creatine kinase to adenine nucleotide translocase was attenuated as evidenced by the decreased effect of creatine on the K-m for ADP in the reactions of oxidative phosphorylation. In m. soleus, a low K-m, for ADP compared to the wild-type counterpart was found, which implies increased permeability for that nucleotide across the mitochondrial outer membrane. In normal cardiac fibers 35% of the ADP flux generated by ATPases was not accessible to the external pyruvate kinase-phosphoenolpyruvate system, which suggests the compartmentalized (direct) channeling of that fraction of ADP to mitochondria. Compared to control, the direct ADP transfer was increased in MDX ventricles. In conclusion. our data indicate that in slow-twitch muscle cells, the absence of dystrophin is associated with the rearrangement of the intracellular energy and feedback signal transfer systems between mitochondria and ATPases. As the mechanisms mediated by creatine kinases become ineffective, the role of diffusion of adenine nucleotides increases due to the higher permeability of the mitochondrial outer membrane for ADP and enhanced compartmentalization of ADP flux. (C) 2001 Elsevier Science B.V. All rights reserved
Ethical aspects of aging research
During the last 50\u201360 years, due to development
of medical care and hygienically safe living
conditions, the average life span of European citizens
has substantially increased, with a rapid growth of the
population older than 65 years. This trend places evergrowing
medical and economical burden on society, as
many of the older subjects suffer from age-related
diseases and frailty. Coping with these problems
requires not only appropriate medical treatment and social support but also extensive research in many
fields of aging\u2014from biology to sociology, with
involvement of older people as the research subjects.
This work anticipates development and application of
ethical standards suited to dynamic advances in aging
research. The aim of this review is to update the
knowledge in ethical requirements toward recruitment
of older research subjects, obtaining of informed
consent, collection of biological samples, and use of
stem cells in preclinical and clinical settings. It is
concluded that application of adequate ethical platform
markedly facilitates recruitment of older persons for
participation in research. Currently, the basic ethical
concepts are subjected to extensive discussion, with
participation of all interested parties, in order to
guarantee successful research on problems of human
aging, protect older people from undesired interference,
and afford their benefits through supporting
innovations in research, therapy, and care
The Importance of Mitochondrial Outer Compartment for Mitochondrial Function under Normal and Impaired (Endotoxin, Ischemia) Conditions
Function of the mitochondrial outer membrane as a diffusion barrier in health and diseases
Intracellular energetic units in red muscle cells.
The kinetics of regulation of mitochondrial respiration by endogenous and exogenous ADP in muscle cells in situ was studied in skinned cardiac and skeletal muscle fibres. Endogenous ADP production was initiated by addition of MgATP; under these conditions the respiration rate and ADP concentration in the medium were dependent on the calcium concentration, and 70-80% of maximal rate of respiration was achieved at ADP concentration below 20 microM in the medium. In contrast, when exogenous ADP was added, maximal respiration rate was observed only at millimolar concentrations. An exogenous ADP-consuming system consisting of pyruvate kinase (PK; 20-40 units/ml) and phosphoenolpyruvate (PEP; 5 mM), totally suppressed respiration activated by exogenous ADP, but the respiration maintained by endogenous ADP was not suppressed by more than 20-40%. Creatine (20 mM) further activated respiration in the presence of ATP and PK+PEP. Short treatment with trypsin (50-500 nM for 5 min) decreased the apparent K(m) for exogenous ADP from 300-350 microM to 50-60 microM, increased inhibition of respiration by PK+PEP system up to 70-80%, with no changes in MgATPase activity and maximal respiration rates. Electron-microscopic observations showed detachment of mitochondria and disordering of the regular structure of the sarcomere after trypsin treatment. Two-dimensional electrophoresis revealed a group of at least seven low-molecular-mass proteins in cardiac skinned fibres which were very sensitive to trypsin and not present in glycolytic fibres, which have low apparent K(m) for exogenous ADP. It is concluded that, in oxidative muscle cells, mitochondria are incorporated into functional complexes ('intracellular energetic units') with adjacent ADP-producing systems in myofibrils and in sarcoplasmic reticulum, probably due to specific interaction with cytoskeletal elements responsible for mitochondrial distribution in the cell. It is suggested that these complexes represent the basic pattern of organization of muscle-cell energy metabolism