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1.
In vitro import studies have confirmed the participation of cytosolic protein factors in the import of various precursor proteins into mitochondria. The requirement for extramitochondrial adenosine triphosphate for the import of a group of precursor proteins seems to be correlated with the chaperone activity of the cytosolic protein factors. One of the cytosolic protein factors is hsp70, which generally recognizes and binds unfolded proteins in the cytoplasm. Hsp70 keeps the newly synthesized mitochondrial precursor proteins in import-competent unfolded conformations. Another cytosolic protein factor that has been characterized is mitochondrial import stimulation factor (MSF), which seems to be specific to mitochondrial precursor proteins. MSF recognizes the mitochondrial precursor proteins, forms a complex with them and targets them to the receptors on the outer surface of mitochondria. 相似文献
2.
Summary We review here the present knowledge about the pathway of import and assembly of porin into mitochondria and compare it to those of other mitochondrial proteins. Porin, like all outer mitochondrial membrane proteins studied so far is made as a precursor without a cleavble signal sequence; thus targeting information must reside in the mature sequence. At least part of this information appears to be located at the amino-terminal end of the molecule. Transport into mitochondria can occur post-translationally. In a first step, the porin precursor is specifically recognized on the mitochondrial surface by a protease sensitive receptor. In a second step, porin precursor inserts partially into the outer membrane. This step is mediated by a component of the import machinery common to the import pathways of precursor proteins destined for other mitochondrial subcompartments. Finally, porin is assembled to produce the functional oligomeric form of an integral membrane protein wich is characterized by its extreme protease resistance. 相似文献
3.
Justo R Alcolea MP Colom B Riera AN Gianotti M García-Palmer FJ 《Cellular and molecular life sciences : CMLS》2002,59(12):2199-2209
To establish the role of mitochondrial subpopulations in the mitochondrial maturation process, we studied morphological and
functional changes in the mitochondria of different mammalian conceptus tissues during the organogenic and the placentation
processes. Mitochondrial subpopulations of three different conceptus tissues, embryo and visceral yolk sac placenta on gestational
days 11, 12 and 13 and placenta on days 12 and 13, were examined morphologically by transmission electron microscopy. Cytochrome
oxidase activity and protein levels were also measured in each mitochondrial subpopulation. The results indicate two different
mitochondrial subpopulation profiles: a homogeneous one, which corresponds to immature mitochondria, and a heterogeneous one,
which represents the mature mitochondria. The three tissues studied show different morphologic and metabolic patterns of mitochondrial
maturation during the placentation process, rendering them suitable as experimental models to establish the p
ossible relationship between mitochondrial maturation and the mitochondrial subpopulations.
Received 5 August 2002; received after revision 23 September 2002; accepted 8 October 2002
RID="*"
ID="*"Corresponding author. 相似文献
4.
Biogenesis of mitochondrial porin: the import pathway. 总被引:2,自引:0,他引:2
We review here the present knowledge about the pathway of import and assembly of porin into mitochondria and compare it to those of other mitochondrial proteins. Porin, like all outer mitochondrial membrane proteins studied so far is made as a precursor without a cleavable 'signal' sequence; thus targeting information must reside in the mature sequence. At least part of this information appears to be located at the amino-terminal end of the molecule. Transport into mitochondria can occur post-translationally. In a first step, the porin precursor is specifically recognized on the mitochondrial surface by a protease sensitive receptor. In a second step, porin precursor inserts partially into the outer membrane. This step is mediated by a component of the import machinery common to the import pathways of precursor proteins destined for other mitochondrial subcompartments. Finally, porin is assembled to produce the functional oligomeric form of an integral membrane protein which is characterized by its extreme protease resistance. 相似文献
5.
The short proline-rich antibacterial peptide family 总被引:16,自引:0,他引:16
Otvos L 《Cellular and molecular life sciences : CMLS》2002,59(7):1138-1150
From the many peptide families that are induced upon bacterial infection and can be isolated from all classes of animals,
the short, proline-rich antibacterial peptides enjoy particular interest. These molecules were shown to inactivate an intracellular
biopolymer in bacteria without destroying or remaining attached to the bacterial cell membrane, and as such emerged as viable
candidates for the treatment of mammalian infections. These peptides were originally isolated from insects, they kill mostly
Gram-negative bacteria with high efficiency and they show structural similarities with longer insect- and mammal-derived antimicrobial
peptides. However, while the distant relatives appear to carry multiple functional domains, apidaecin, drosocin, formaecin
and pyrrhocoricin consist of only minimal determinants needed to penetrate across the cell membrane and bind to the target
biopolymer. These peptides appear to inhibit metabolic processes, such as protein synthesis or chaperone-assisted protein
folding. Pyrrhocoricin derivatives protect mice from experimental infections in vivo, suggesting the utility of modified analogs
in the clinical setting. Sequence variations of the target protein at the peptide-binding site may allow the development of
new peptide variants that kill currently unresponsive strains or species.
Received 12 December 2001; received after revision 11 February 2002; accepted 19 February 2002 相似文献
6.
Cancer cell metabolism is characterized by limited oxidative phosphorylation in order to minimize oxidative stress. We have
previously shown that the flavonoid flavone in HT-29 colon cancer cells increases the uptake of pyruvate or lactate into mitochondria,
which is followed by an increase in O2−.. production that finally leads to apoptosis. Similarly, a supply of palmitoylcarnitine in combination with carnitine induces
apoptosis in HT-29 cells by increasing the mitochondrial respiration rate. Here we show that flavone-induced apoptosis is
increased more than twofold in the presence of palmitoylcarnitine due to increased mitochondrial fatty acid transport and
the subsequent metabolic generation of O2−. in mitochondria is the initiating factor for the execution of apoptosis.
Received 12 August 2005; received after revision 12 October 2005; accepted 14 October 2005 相似文献
7.
Mollica MP Lionetti L Crescenzo R D'Andrea E Ferraro M Liverini G Iossa S 《Cellular and molecular life sciences : CMLS》2006,63(3):358-366
This study was designed to examine energetic behaviour of skeletal muscle subsarcolemmal and intermyofibrillar mitochondrial
populations. The data show that subsarcolemmal mitochondria exhibited a lower degree of coupling and efficiency than intermyofibrillar
ones, and can therefore be considered less efficient at producing ATP. In addition, subsarcolemmal mitochondria showed an
increased sensitivity to palmitate-induced uncoupling, in line with high adenine nucleotide translocator content and decreased
oxidative damage. We then determined the effect of 24 h fasting on energetic characteristics of skeletal muscle mitochondrial
populations. We found that fasting enhanced proton leak and decreased the degree of coupling and efficiency, both in the absence
and in the presence of palmitate only in subsarcolemmal mitochondria. Moreover, this mitochondrial population showed lower
oxidative damage, probably due to a counter-regulatory mechanism mediated by uncoupling protein 3. Subsarcolemmal and intermyofibrillar
mitochondria appear to exhibit different energetic characteristics and can be differently affected by physiological stimuli.
Received 28 September 2005; received after revision 9 November 2005; accepted 28 November 2005 相似文献
8.
Parihar MS Parihar A Fujita M Hashimoto M Ghafourifar P 《Cellular and molecular life sciences : CMLS》2008,65(7-8):1272-1284
α-Synuclein is a neuron-specific protein that contributes to the pathology of Parkinson’s disease via mitochondria-related mechanisms. The present study investigated possible interaction of α-synuclein with mitochondria and
consequences of such interaction. Using SHSY cells overexpressing α-synuclein A53T mutant or wild-type, as well as isolated
rat brain mitochondria, the present study shows that α-synuclein localizes at the mitochondrial membrane. In both SHSY cells
and isolated mitochondria, interaction of α-synuclein with mitochondria causes release of cytochrome c, increase of mitochondrial calcium and nitric oxide, and oxidative modification of mitochondrial components. These findings
suggest a pivotal role for mitochondria in oxidative stress and apoptosis induced by α-synuclein.
Received 27 December 2007; received after revision 7 February 2008; accepted 8 February 2008 相似文献
9.
Evidence of undiscovered cell regulatory mechanisms: phosphoproteins and protein kinases in mitochondria 总被引:3,自引:0,他引:3
Thomson M 《Cellular and molecular life sciences : CMLS》2002,59(2):213-219
The finding that mitochondria contain substrates for protein kinases lead to the discovery that protein kinases are located
in the mitochondria of certain tissues and species. These include pyruvate dyhydrogenase kinase, branched-chain α-ketoacid dehydrogenase kinase, protein kinase A, protein kinase Cδ, stress-activated kinase and A-Raf as well as unidentified kinases. Recent evidence suggests that mitochondrial protein kinases
may be involved in physiological processes such as apoptosis and steroidogenesis. Additionally, the novel finding of low-molecular-weight
GTP-binding proteins in mitochondria suggests the possibility that these may interact with mitochondrial protein kinases to
regulate the activity of mitochondrial effector proteins. The fact that there are components of cellular regulatory systems
in mitochondria indicates the exciting possibility of undiscovered systems regulating mitochondrial physiology.
Received 19 June 2001; received after revision 7 August 2001; accepted 8 August 2001 相似文献
10.
11.
Identification of tyrosine-phosphorylated proteins of the mitochondrial oxidative phosphorylation machinery 总被引:1,自引:1,他引:0
Augereau O Claverol S Boudes N Basurko MJ Bonneu M Rossignol R Mazat JP Letellier T Dachary-Prigent J 《Cellular and molecular life sciences : CMLS》2005,62(13):1478-1488
The role of some serine/threonine kinases in the regulation of mitochondrial physiology is now well established, but little is known about mitochondrial tyrosine kinases. We showed that tyrosine phosphorylation of rat brain mitochondrial proteins was increased by in vitro addition of ATP and H2O2, and also during in situ ATP production at state 3, and maximal reactive oxygen species production. The Src kinase inhibitor PP2 decreased tyrosine phosphorylation and respiratory rates at state 3. We found that the 39-kDa subunit of complex I was tyrosine phosphorylated, and we identified putative tyrosine-phosphorylated subunits for the other complexes. We also have strong evidence that the FoF1-ATP synthase α chain is probably tyrosine-phosphorylated, but demonstrated that the β chain is not. The tyrosine phosphatase PTP 1B was found in brain but not in muscle, heart or liver mitochondria. Our results suggest that tyrosine kinases and phosphatases are involved in the regulation of oxidative phosphorylation.Received 7 January 2005; received after revision 19 April 2005; accepted 22 April 2005 相似文献
12.
Regulation of mitochondrial oxidative phosphorylation by second messenger-mediated signal transduction mechanisms 总被引:2,自引:0,他引:2
Boneh A 《Cellular and molecular life sciences : CMLS》2006,63(11):1236-1248
The mitochondrial oxidative phosphorylation system is responsible for providing the bulk of cellular ATP molecules. There
is a growing body of information regarding the regulation of this process by a number of second messenger-mediated signal
transduction mechanisms, although direct studies aimed at elucidating this regulation are limited. The main second messengers
affecting mitochondrial signal transduction are cAMP and calcium. Other second messengers include ceramide and reactive oxygen
species as well as nitric oxide and reactive nitrogen species. This review focuses on available data on the regulation of
the mitochondrial oxidative phosphorylation system by signal transduction mechanisms and is organised according to the second
messengers involved, because of their pivotal role in mitochondrial function. Future perspectives for further investigations
regarding these mechanisms in the regulation of the oxidative phosphorylation system are formulated.
Received 11 December 2005; received after revision 14 January 2006; accepted 6 February 2006 相似文献
13.
M. Dihanich 《Cellular and molecular life sciences : CMLS》1990,46(2):146-153
Summary Like most other mitochondrial proteins porin is synthesized in the cytosol and imported posttranslationally into the outer mitochondrial membrane. This transport follows the general rules for mitochondrial, protein import with a few aberrations: a) porin contains an,uncleaved NH2-terminal signal sequence, b) also its carboxyterminus might be involved in the import process, and c) this transport does not seem to require a membrane potential , although it is ATP-dependent. Most likely the actual import step occurs at contact sites between the outer and the inner mitochondrial membrane and involved at least one receptor protein.Although porin is known to be the major gate through the outer mitochondrial membrane, its absence only causes transient respiratory problems in yeast cells. This could mean a) that there is a bypass for some mitochondrial functions in the cytosol and/or b) that there are alternative channel proteins in the outer membrane. The first idea is supported by the overexpression of cytosolic virus-like particles in yeast cells lacking porin and the second by the occurrence of residual pore activity in mitochondrial outer membrane purified from porinless mutant cells. 相似文献
14.
Role of nitric oxide in the functional response to ischemia-reperfusion of heart mitochondria from hyperthyroid rats 总被引:2,自引:0,他引:2
Venditti P De Rosa R Cigliano L Agnisola C Di Meo S 《Cellular and molecular life sciences : CMLS》2004,61(17):2244-2252
We investigated the role of nitric oxide (NO) in the mitochondrial derangement associated with the functional response to ischemia-reperfusion of hyperthyroid rat hearts. Mitochondria were isolated at 3000 g from hearts subjected to ischemia-reperfusion, with or without N-nitro-L-arginine (L-NNA, an NO synthase inhibitor). During reperfusion, hyperthyroid hearts displayed tachycardia and low functional recovery. Their mitochondria exhibited O2 consumption similar to euthyroid controls, while H2O2 production, hydroperoxide, protein-bound carbonyl and nitrotyrosine levels, and susceptibility to swelling were higher. L-NNA blocked the reperfusion tachycardic response and increased inotropic recovery in hyperthyroid hearts. L-NNA decreased mitochondrial H2O2 production and oxidative damage, and increased respiration and tolerance to swelling. Such effects were higher in hyperthyroid preparations. These results confirm the role of mitochondria in ischemia-reperfusion damage, and strongly suggest that NO overproduction is involved in the high mitochondrial dysfunction and the low recovery of hyperthyroid hearts from ischemia-reperfusion. L-NNA also decreased protein content and cytochrome oxidase activity of a mitochondrial fraction isolated at 8000 g. This and previous results suggest that the above fraction contains, together with light mitochondria, damaged mitochondria coming from the heaviest fraction, which has the highest cytochrome oxidase activity and capacity to produce H2O2. Therefore, we propose that the high mitochondrial susceptibility to swelling, favoring mitochondrial population purification from H2O2-overproducing mitochondria, limits hyperthyroid heart oxidative stress.Received 24 March 2004; received after revision 9 June 2004; accepted 5 July 2004 相似文献
15.
The venoms of predatory cone snails (genus Conus) have yielded a complex library of about 50–100,000 bioactive peptides, each believed to have a specific physiological target
(although peptides from different species may overlap in their target specificity). Conus has evolved the equivalent of a drug development strategy that combines the accelerated evolution of toxin sequences with
an unprecedented degree of posttranslational modification. Some Conus venom peptide families are the most highly posttranslationally modified classes of gene products known. We review the variety
and complexity of posttranslational modifications documented in Conus peptides so far, and explore the potential of Conus venom peptides as a model system for a more general understanding of which secreted gene products may have modified amino
acids. Although the database of modified conotoxins is growing rapidly, there are far more questions raised than answers provided
about possible mechanisms and functions of posttranslational modifications in Conus.
Received 24 June 2005; received after revision 13 August 2005; accepted 19 September 2005 相似文献
16.
Effects of myocardial ischemia and reperfusion on mitochondrial function and susceptibility to oxidative stress 总被引:8,自引:0,他引:8
We investigated the effects of ischemia duration on the functional response of mitochondria to reperfusion and its relationship
with changes in mitochondrial susceptibility to oxidative stress. Mitochondria were isolated from hearts perfused by the Langendorff
technique immediately after different periods of global ischemia or reperfusion following such ischemia periods. Rates of
O2 consumption and H2O2 release with complex I- and complex II-linked substrates, lipid peroxidation, overall antioxidant capacity, capacity to remove
H2O2, and susceptibility to oxidative stress were determined. The effects of ischemia on some parameters were time dependent so
that the changes were greater after 45 than after 20 min of ischemia, or were significantly different to the nonischemic control
only after 45 min of ischemia. Thus, succinate-supported state 3 respiration exhibited a significant decrease after 20 min
of ischemia and a greater decrease after 45 min, while pyruvate malate-supported respiration showed a significant decrease
only after 45 min of ischemia, indicating an ischemia-induced early inhibition of complex II and a late inhibition of complex
I. Furthermore, both succinate and pyruvate malate-supported H2O2 release showed significant increases only after 45 min of ischemia. Similarly, whole antioxidant capacity significantly increased
and susceptibility to oxidants significantly decreased after 45 min of ischemia. Such changes were likely due to the accumulation
of reducing equivalents, which are able to remove peroxides and maintain thiols in a reduced state. This condition, which
protects mitochondria against oxidants, increases mitochondrial production of oxyradicals and oxidative damage during reperfusion.
This could explain the smaller functional recovery of the tissue and the further decline of the mitochondrial function after
reperfusion following the longer period of oxygen deprivation.
Received 18 May 2001; received after revision 17 July 2001; accepted 24 July 2001 相似文献
17.
Summary The mitochondrial division ofPhysarum is inhibited by cytochalasin B. Dumbbell-shaped dividing mitochondria become spherical bodies by this inhibitor. These results suggest that contractile proteins are essential for the mitochondrial division. 相似文献
18.
Optic atrophy 3 as a protein of the mitochondrial outer membrane induces mitochondrial fragmentation
Seung-Wook Ryu Hyeon Joo Jeong Myunghwan Choi Mariusz Karbowski Chulhee Choi 《Cellular and molecular life sciences : CMLS》2010,67(16):2839-2850
The optic atrophy 3 (OPA3) gene, which has no known homolog or biological function, is mutated in patients with hereditary
optic neuropathies. Here, we identified OPA3 as an integral protein of the mitochondrial outer membrane (MOM), with a C-terminus
exposed to the cytosol and an N-terminal mitochondrial targeting domain. By quantitative analysis, we demonstrated that overexpression
of OPA3 significantly induced mitochondrial fragmentation, whereas OPA3 knockdown resulted in highly elongated mitochondria.
Cells with mitochondria fragmented by OPA3 did not undergo spontaneous apoptotic cell death, but were significantly sensitized
to staurosporine- and TRAIL-induced apoptosis. In contrast, overexpression of a familial OPA3 mutant (G93S) induced mitochondrial
fragmentation and spontaneous apoptosis, suggesting that OPA3 mutations may cause optic atrophy via a gain-of-function mechanism.
Together, these results indicate that OPA3, as an integral MOM protein, has a crucial role in mitochondrial fission, and provides
a direct link between mitochondrial morphology and optic atrophy. 相似文献
19.
Plasticins belong to the dermaseptin superfamily of gene-encoded, membrane-active host defense peptides produced by the skin
of hylid frogs. The plasticins, which are rich in Gly and Leu residues arranged in regular 5-mer motifs GXXXG (where X is
any amino acid residue), have very similar amino acid sequences, hydrophobicities, and amphipathicities but differ markedly
in their net charge, conformational plasticity, and activity spectra. The intrinsic flexibility and structural malleability
of plasticins modulate their ability to bind to and disrupt the membranes of prokaryotic and eukaryotic cells, and/or to reach
intracellular targets, therefore triggering functional versatility. This family of closely related but functionally divergent
peptides constitutes a good model to address the relationships between structural polymorphism, membrane-interacting properties,
and the biological activity of antimicrobial, cell-penetrating, and viral fusion peptides. Plasticins could thus serve as
templates to design potent multifunctional drugs that could act simultaneously against bacterial pathogens and viruses.
Received 26 September 2007; received after revision 22 October 2007; accepted 29 October 2007 相似文献
20.
T. L. Mason C. Pan M. E. Sanchirico K. Sirum-Connolly 《Cellular and molecular life sciences : CMLS》1996,52(12):1148-1157
Mitochondria posses their own ribosomes responsible for the synthesis of a small number of proteins encoded by the mitochondrial genome. In yeast,Saccharomyces cerevisiae, the two ribosomal RNAs and a single ribosomal protein, Varl, are products of mitochondrial genes, and the remaining approximately 80 ribosomal proteins are encoded in the nucleus. The mitochondrial translation system is dispensable in yeast, providing an excellent experimental model for the molecular genetic analysis of the fundamental properties of ribosomes in general as well as adaptations required for the specialized role of ribosomes in mitochondria. Recent studies of the peptidyl transferase center, one of the most highly conserved functional centers of the ribosome, and the Varl protein, an unusual yet essential protein in the small ribosomal subunit, have provided new insight into conserved and divergent features of the mitochondrial ribosome. 相似文献