Mitochondrial targeting signals processes

It has recently been demonstrated that processing of P450 IBl by a cytosolic serine protease activates a mitochondrial-targeting signal of P450 IBl and leads to mitochondrial localization and activity, where functional activity results from coupling with the adrenodoxin electron delivery system [340]. 

This a-helix is amphipathic, containing patches of positively charged and hydrophobic amino acids, respectively, on opposite surfaces of the theoretical cylinder. The presequence is usually processed by the mitochondrial processing peptidase (MPP) and the mature protein is sorted to either the matrix, or to the inner membrane if it bears a hydrophobic stop-transfer sequence. Some mitochondrial proteins, mostly destined to the membranes, do not have cleavable N-terminal presequences but have internal targeting signals that are not well characterized (Pfanner and Geissler 2001). 

During the process of cell death, cytochrome c is released from mitochondria into the cytosol where it assists to activate the caspases, a family of killer caspases that trigger cell death, hi this chapter evidence that transmission of cell death signals into the release of cytochrome c involves phospholipids at several stages will be presented. Thus, phospholipids target proapoptotic proteins to mitochondria, enable these or other proteins to form channels or pores and to break the mitochondrial permeability barrier. Finally, peroxidation or increased levels of disrupt the ability of cardiolipin to interact with cytochrome c, initiating a sequence of events that ultimately lead to cell death. 

Most mitochondria and chloroplast proteins are made on free cytosolic ribosomes, released into the cytosol and then taken up into the organelle. Uptake into the mitochondrial matrix requires a matrix-targeting sequence and occurs at sites where the outer and inner mitochondrial membranes come into contact. The process is mediated by hsp70 and hsp60 proteins and requires both ATP hydrolysis and an electrochemical gradient across the inner mitochondrial membrane. Targeting of proteins to other compartments of mitochondria or chloroplasts requires two signals. 

Ott M, Robertson JD, Gogvadze V,Zhivotovsky B, Orrenius S (2002) Cytochrome c release from mitochondria proceeds by a two-step process. Proc Natl Acad Sci USA 99 1259-1263 Schroeter H, Boyd CS, Ahmed R, Spencer JPE, Duncan RF, Rice-Evans C, Cadenas E (2003) JNK-mediated modulation of brain mitochondria function new target proteins for JNK-signaling in mitochondria-dependent apoptosis. Biochem J 372 359-369 Alvarez S, Valdez LB,Zaobornyj T, Boveris A (2003) Oxygen dependence of mitochondrial nitric oxide synthase activity. Biochem Biophys Res Commun 305 771-775... 

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