tailieunhanh - Báo cáo khoa học: The molecular identity of the mitochondrial Ca2+ sequestration system

The role of non-B DNA in the function and stability of genomes has become generally appreciated in recent years. It is now evident that DNA also encodes for spatial structures that are involved in gene regulation, replication and recombination. | MINIREVIEW The molecular identity of the mitochondrial Ca2 sequestration system Anatoly A. Starkov WeillMedicalCollege of CornellUniversity New York NY USA Keywords brain mitochondria Ca2 accumulation Ca2 and Pi precipitate calciphorin calcium uniporter calvectin dense granules gC1qR liver mitochondria permeability transition pore Correspondence A. A. Starkov 1300 York Ave A501 New York NY 10065 USA Fax 1 212 746 8276 Tel 1 212 746 4534 E-mail ans2024@ Received 8 March 2010 revised 23 May 2010 accepted 23 June 2010 There is ample evidence to suggest that a dramatic decrease in mitochondrial Ca2 retention may contribute to the cell death associated with stroke excitotoxicity ischemia and reperfusion and neurodegenerative diseases. Mitochondria from all studied tissues can accumulate and store Ca2 but the maximum Ca2 storage capacity varies widely and exhibits striking tissue specificity. There is currently no explanation for this fact. Precipitation of Ca2 and phosphate in the mitochondrial matrix has been suggested to be the major form of storage of accumulated Ca2 in mitochondria. How this precipitate is formed is not known. The molecular identity of almost all proteins involved in Ca2 transport storage and formation of the permeability transition pore is also unknown. This review summarizes studies aimed at identifying these proteins and describes the properties of a known mitochondrial protein that may be involved in Ca2 transport and the structure of the permeability transition pore. doi The standard model The ability to accumulate retain and release Ca2 is a fundamental ubiquitous function of animal mitochondria. Extensive research during the last 50 years has resulted in a consensus model of mitochondrial Ca2 handling that adequately accommodates most if not all experimental data referred to here as the standard model of mitochondrial Ca2 handling . This model is shown in Fig. 1 in a greatly simplified form and