TAILIEUCHUNG - Báo cáo khoa học: Bax distribution into mitochondrial detergent-resistant microdomains is related to ceramide and cholesterol content in postischemic hearts

Diverse changes have been described in mitochondria of apoptotic cells: the phospholipid content is modified, ceramide and GD3 concentrations increase, the cristae structure is modified, and nonresident proteins are recruited into the mitochondrial membranes. In particular, Bax, a Bcl-2 family member protein, moves from the cytosol to the mitochondria, inducing cytochrome c release. | ỊFEBS Journal Bax distribution into mitochondrial detergent-resistant microdomains is related to ceramide and cholesterol content in postischemic hearts Eduardo Martinez-Abundis Francisco Correa Natalia Pavon and Cecilia Zazueta Departamento de Bioquímica Institute Nacionalde Cardiologia Ignacio Chavez Juan Badiano No. 1 Col. Seccion XVI Mexico City Mexico Keywords Bax ceramide cholesterol intrinsic apoptosis mitochondriallipid microdomains Correspondence C. Zazueta Departamento de Bioquímica Instituto Nacionalde Cardiología I. Ch. Juan Badiano No. 1 Colonia Seccion XVI Mexico City 14080 . Mexico Fax 52 55 5573 0926 Tel 52 55 5573 2911 1298 E-mail azazuetam@ Received 12 June 2009 revised 16 July 2009 accepted 27 July 2009 doi Diverse changes have been described in mitochondria of apoptotic cells the phospholipid content is modified ceramide and GD3 concentrations increase the cristae structure is modified and nonresident proteins are recruited into the mitochondrial membranes. In particular Bax a Bcl-2 family member protein moves from the cytosol to the mitochondria inducing cytochrome c release. Modifications of the content and distribution of specific lipids in the mitochondrial membranes along with the well-known participation of the mitochondrial permeability transition pore in triggering apoptosis led us to propose that lipid microdomains in mitochondria could coexist as structural elements with some of the mitochondrial permeability transition pore-forming proteins and with members of the Bcl-2 family. In this work we demonstrated that Bax was associated preferentially with mitochondrial detergent-resistant membranes mDRMs in reperfused rat hearts a well-known apoptotic model. Bax insertion into mDRMs correlated with cytochrome c release from such mitochondria. Bax location in mDRMs was associated with both the voltage-dependent anion channel and the adenine nucleotide translocator two mitochondrial permeability .

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