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The regulator of calcineurin 1 increases adenine nucleotide translocator 1 and leads to mitochondrial dysfunctions
Author(s) -
Jiang Hui,
Zhang Chen,
Tang Yu,
Zhao Juan,
Wang Tan,
Liu Heng,
Sun Xiulian
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13900
Subject(s) - adenine nucleotide translocator , mitochondrion , gene knockdown , microbiology and biotechnology , biology , regulator , mitochondrial permeability transition pore , calcineurin , atp–adp translocase , translocator protein , inner mitochondrial membrane , ant , dnaja3 , mitochondrial apoptosis induced channel , apoptosis , programmed cell death , mitochondrial dna , mitochondrial fusion , biochemistry , gene , immunology , medicine , ecology , transplantation , neuroinflammation , inflammation , surgery
The over‐expression of regulator of calcineurin 1 isoform 1 ( RCAN 1.1) has been implicated in mitochondrial dysfunctions of Alzheimer's disease; however, the mechanism linking RCAN 1.1 over‐expression and the mitochondrial dysfunctions remains unknown. In this study, we use human neuroblastoma SH ‐ SY 5Y cells stably expressing RCAN 1.1S and rat primary neurons infected with RCAN 1.1S expression lentivirus to study the association of RCAN 1 with mitochondrial functions. Our study here showed that the over‐expression of RCAN 1.1S remarkably up‐regulates the expression of adenine nucleotide translocator ( ANT 1) by stabilizing ANT 1 mRNA . The increased ANT 1 level leads to accelerated ATP – ADP exchange rate, more Ca 2+ ‐induced mitochondrial permeability transition pore opening, increased cytochrome c release, and eventually cell apoptosis. Furthermore, knockdown of ANT 1 expression brings these mitochondria perturbations caused by RCAN 1.1S back to normal. The effect of RCAN 1.1S on ANT 1 was independent of its inhibition on calcineurin. This study elucidated a novel function of RCAN 1 in mitochondria and provides a molecular basis for the RCAN 1.1S over‐expression‐induced mitochondrial dysfunctions and neuronal apoptosis.