Refractive Index Imaging Reveals That Elimination of the ATP Synthase C Subunit Does Not Prevent the Adenine Nucleotide Translocase-Dependent Mitochondrial Permeability Transition.
Refractive Index Imaging Reveals That Elimination of the ATP Synthase C Subunit Does Not Prevent the Adenine Nucleotide Translocase-Dependent Mitochondrial Permeability Transition.
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DOI：
10.3390/cells12151950
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发表时间：
2023-07-27
期刊：
影响因子：
6
通讯作者：
Pavlov, Evgeny V. V.
中科院分区：
文献类型：
--
作者：
Neginskaya, Maria A. A.;Morris, Sally E. E.;Pavlov, Evgeny V. V.
关键词：
线粒体通透性过渡孔（mPTP）是一个大的、弱选择性的孔，在线粒体内膜上开放，以响应病理基质Ca2+浓度的增加。mPTP激活被认为是应激诱导的坏死和凋亡细胞死亡的关键因素。mPTP的分子特性尚不完全清楚。ATP合成酶和腺嘌呤核苷酸转位酶（ANT）都被认为是mPTP的重要组成部分。使用折射率（RI）成像方法，我们最近证明，去除ATP合酶或ANT消除Ca2+诱导的mPTP在完整细胞的实验中。这些结果表明mPTP的形成依赖于ATP合酶和ANT蛋白复合物之间的相互作用。为了进一步了解这一过程，我们使用RI成像技术研究了具有遗传消除ATP合酶C亚基的细胞的mPTP特性。这些细胞也缺乏ATP6、ATP8、6.8PL亚基和DAPIT，但重要的是，它们有一个退化的ATP合成酶复合物，具有组装的F1和外周茎结构域。我们发现这些细胞仍然可以经历mPTP激活，这可以被ANT抑制剂bongkrekic酸阻断。这些结果表明，ANT可以独立于C亚基形成孔，但仍然需要ATP合酶的其他组分的存在。
The mitochondrial permeability transition pore (mPTP) is a large, weakly selective pore that opens in the mitochondrial inner membrane in response to the pathological increase in matrix Ca2+ concentration. mPTP activation has been implicated as a key factor contributing to stress-induced necrotic and apoptotic cell death. The molecular identity of the mPTP is not completely understood. Both ATP synthase and adenine nucleotide translocase (ANT) have been described as important components of the mPTP. Using a refractive index (RI) imaging approach, we recently demonstrated that the removal of either ATP synthase or ANT eliminates the Ca2+-induced mPTP in experiments with intact cells. These results suggest that mPTP formation relies on the interaction between ATP synthase and ANT protein complexes. To gain further insight into this process, we used RI imaging to investigate mPTP properties in cells with a genetically eliminated C subunit of ATP synthase. These cells also lack ATP6, ATP8, 6.8PL subunits and DAPIT but, importantly, have a vestigial ATP synthase complex with assembled F1 and peripheral stalk domains. We found that these cells can still undergo mPTP activation, which can be blocked by the ANT inhibitor bongkrekic acid. These results suggest that ANT can form the pore independently from the C subunit but still requires the presence of other components of ATP synthase.
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作者：
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通讯作者：
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影响因子：
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DOI：
10.1073/pnas.1401591111
发表时间：
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10.1073/pnas.1711201114
发表时间：
2017-08-22
影响因子：
11.1
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通讯作者：
Walker, John E.