Mitochondrial heat shock protein

Truscott KN et al. (2001) A presequence- and voltage-sensitive channel of the mitochondrial preprotein translocase formed by Tim23. Nat Struct Biol 8 1074-1082 Truscott KN et al. (2003) A J-protein is an essential subunit of the presequence translocase-associated protein import motor of mitochondria. J Cell Biol 163 707-713 van der Giezen M et al. (2003) Fungal hydrogenosomes contain mitochondrial heat-shock proteins. Mol Biol Evol 20 1051-1061... 

Cheng, M.Y., F. U. Hard, J. Martin, R. A. Pollock, F. Kalousek, W. Neupert, E. M. Hallberg, R. L. Hallberg, and A. L. Horwich (1989). Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported into yeast mitochondria. Nature 337, 620-625. 

Fig. 20.20. Model for the import of nuclear-encoded proteins into the mitochondrial matrix. The matrix preprotein with its positively charged N-terminal presequence is shown in blue. Abbreviations OM, outer mitochondrial membrane IMS, intramembrane space IM, inner mitochondrial membrane TOM, translocases of the outer mitochondrial membrane TIM, translocases of the inner mitochondrial membrane mthspTO, mitochondrial heat shock protein 70.

Figure 3. Schematic architecture of mitochondrial protein complexes. A transmembrane channel, called the permeability transition pore (FTP), is formed at the contaa sites between the inner and outer mitochondrial membrane (OM) of the mitochondria. The core components of PTP are the voltage-dependent anion channel (VDAC) in the outer membrane and the adenine nucleotide translocator (ANT) in the inner membrane (IM). VDAC allows diilusion of small molecules (<5 kDa), however ANT is only permeable to a few selected ions and metabolites and is responsible for maintaining the proton concentration gradient (pH) and the membrane elearic potential (A P,J. PTP is sometimes connected to destruction of permeability barrier and loss of the inner membrane potential and eventually results in mitochondrial membrane permeability transition during apoptosis and other specialized forms of cell death. Bax, Bak, Bc1-Xl and Bcl-2 locate in the outer membrane and may regulate the outer membrane permeability. The translocase of the outer membrane (TOM) and the translocase of the inner membrane (TlM) mediate protein import pathway in the mitochondria. Cy-D, cyclophilin D PBR, peripheral benzodiazepine receptor HK, hexokinase mtHSP70, mitochondrial heat shock protein 70.

Antiapoptotic proteins. There are many different intracellular proteins that can prevent apoptosis by inhibiting specific steps in the cell death process. These include Bcl-2 family members such as Bcl-2 and Bcl-xL which can stabilize (mitochondrial, ER and plasma) membranes (Bcl-2 may also have intrinsic antioxidant activity). Other proteins, IAPs such as XIAP (X-linked) and NIAP (neuronal), which can directly inhibit caspases [31]. Additional examples of antiapoptotic proteins include protease inhibitors such as calpastatin, and protein chaperones such as GRP-78 and heat shock protein (HSP)-70. 

Clark CG, Roger AJ (1995) Direct evidence for secondary loss of mitochondria in Entamoeba histolytica. Proc Natl Acad Sci USA 92 6518-6521 Claras MG, Vincens P (1996) Computational method to predict mitochondrially imported proteins and their targeting sequences. Eur J Biochem 241 779-786 Craig EA, Kramer J, Kosic-Smithers J (1987) SSC1, a member of the 70-kDa heat shock protein multigene family of Saccharomyces cerevisiae, is essential for growth. Proc Natl Acad Sci USA 84 4156-4160... 

Germot A, Philippe H, Le Guyader H (1996) Presence of a mitochondrial-type 70-kDa heat shock protein in Trichomonas vaginalis suggests a very early mitochondrial en-dosymbiosis in eukaryotes. Proc Natl Acad Sci USA 93 14614-14617... 

Calabrese Y, Colombrita C, Sultana R, Scapagnini G, Calvani M, Butterfield DA, Stella AM. 2006c. Redox modulation of heat shock protein expression by acetylcarnitine in aging brain Relationship to antioxidant status and mitochondrial function. Antioxid Redox Signal 8 404-416. 

Metabonomics Mito stress 70 protein pi ATP synthesis a chain Heats shock protein (HSP) 10 HSP 60 Mitochondrial thioredox-dependent peroxide reductase Mitochondrial matrix protein pi... 

Mitochondrial effects GSH depletion ATP depletion Phospholipid modifications Heat shock protein modifications Lipid peroxidation Inhibition of membrane potential Ca release into cytosol... 

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