کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10802316 1055684 2013 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The role of calcium in VDAC1 oligomerization and mitochondria-mediated apoptosis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
The role of calcium in VDAC1 oligomerization and mitochondria-mediated apoptosis
چکیده انگلیسی
The voltage-dependent anion channel (VDAC), located at the outer mitochondria membrane (OMM), mediates interactions between mitochondria and other parts of the cell by transporting anions, cations, ATP, Ca2 +, and metabolites. Substantial evidence points to VDAC1 as being a key player in apoptosis, regulating the release of apoptogenic proteins from mitochondria, such as cytochrome c, and interacting with anti-apoptotic proteins. Recently, we demonstrated that VDAC1 oligomerization is a general mechanism common to numerous apoptogens acting via different initiating cascades and proposed that a protein-conducting channel formed within a VDAC1 homo/hetero oligomer mediates cytochrome c release. However, the molecular mechanism responsible for VDAC1 oligomerization remains unclear. Several studies have shown that mitochondrial Ca2 + is involved in apoptosis induction and that VDAC1 possesses Ca2 +-binding sites and mediates Ca2 + transport across the OMM. Here, the relationship between the cellular Ca2 + level, [Ca2 +]i, VDAC1 oligomerization and apoptosis was studied. Decreasing [Ca2 +]i using the cell-permeable Ca2 + chelating reagent BAPTA-AM was found to inhibit VDAC1 oligomerization and apoptosis, while increasing [Ca2 +]i using Ca2 + ionophore resulted in VDAC1 oligomerization and apoptosis induction in the absence of apoptotic stimuli. Moreover, induction of apoptosis elevated [Ca2 +]i, concomitantly with VDAC1 oligomerization. AzRu-mediated inhibition of mitochondrial Ca2 + transport decreased VDAC1 oligomerization, suggesting that mitochondrial Ca2 + is required for VDAC1 oligomerization. In addition, increased [Ca2 +]i levels up-regulate VDAC1 expression. These results suggest that Ca2 + promotes VDAC1 oligomerization via activation of a yet unknown signaling pathway or by increasing VDAC1 expression, leading to apoptosis. This article is part of a Special Issue entitled: 12th European Symposium on Calcium.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1833, Issue 7, July 2013, Pages 1745-1754
نویسندگان
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