tailieunhanh - Báo cáo khoa hoc : Dual localization of glutathione S-transferase in the cytosol and mitochondria: implications in oxidative stress, toxicity and disease

Glutathione (GSH) conjugating enzymes, glutathioneS-transferases (GSTs), are present in different subcellular compartments including cytosol, mitochondria, endoplasmic reticulum, nucleus and plasma membrane. The regulation and function of GSTs have implications in cell growth, oxidative stress as well as disease progression and prevention. | fFEBS Journal MINIREVIEW Dual localization of glutathione S-transferase in the cytosol and mitochondria implications in oxidative stress toxicity and disease Haider Raza Department of Biochemistry Faculty of Medicine and Health Sciences UAE University Al Ain UAE Keywords chemical toxicity cryptic mitochondrial signal dual localization of GSTs glutathione S-transferase Hsp70 chaperone N-terminal signal region oxidative stress PKA phosphorylation Correspondence Haider Raza Department of Biochemistry Faculty of Medicine and Health Sciences UAE University PO Box 17666 Al An UAE. Fax 971 3 7672033 Tel 971 3 7137506 E-mail Received 19 May 2011 revised 12 August 2011 accepted 12 September 2011 doi Glutathione GSH conjugating enzymes glutathione S-transferases GSTs are present in different subcellular compartments including cytosol mitochondria endoplasmic reticulum nucleus and plasma membrane. The regulation and function of GSTs have implications in cell growth oxidative stress as well as disease progression and prevention. Of the several mitochondria localized forms GSTK GST kappa is mitochondria-specific since it contains N-terminal canonical and cleavable mitochondria targeting signals. Other forms like GST alpha mu and pi purified from mitochondria are similar to the cytosolic molecular forms or echoproteins . Altered GST expression has been implicated in hepatic cardiac and neurological diseases. Mitochondria-specific GSTK has also been implicated in obesity diabetes and related metabolic disorders. Studies have shown that silencing the GSTA4 GST alpha gene resulted in mitochondrial dysfunction as was also seen in GSTA4 null mice which could contribute to insulin resistance in type 2 diabetes. This review highlights the significance of the mitochondrial GST pool particularly the mechanism and significance of dual targeting of GSTA4-4 under in vitro and in vivo conditions. GSTA4-4 is targeted in the mitochondria by .