Protective Role of Transient Pore Openings in Calcium Handling by Cardiac Mitochondria
Protective Role of Transient Pore Openings in Calcium Handling by Cardiac Mitochondria
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DOI：
10.1074/jbc.m111.239921
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发表时间：
2011-10-07
影响因子：
4.8
通讯作者：
Weiss, James N.
中科院分区：
文献类型：
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作者：
Korge, Paavo;Yang, Ling;Weiss, James N.
长期的线粒体渗透性转换孔（mPTP）开放损伤线粒体，但短暂的mPTP开放保护慢性心脏应激。为了探索机制，我们进行了分离的心肌线粒体逐渐Ca2+负荷，这在BSA的情况下，诱导持久的mPTP开放，引起基质去极化。然而，与BSA模拟细胞质脂肪酸结合蛋白，线粒体人口保持极化和功能，即使在基质Ca 2+释放引起线粒体外游离[Ca 2 +]增加到>10 μ M，除非mPTP开口被抑制。这些发现可以解释为异步瞬时mPTP开放，允许单个线粒体去极化足够长的时间来冲洗积累的基质Ca 2+，然后在孔关闭后迅速恢复。因为随后通过Ca2+单向转运体的基质Ca2+再摄取估计比通过mPTP的基质Ca2+释放慢> 100倍，所以只有很小一部分线粒体（
Long-lasting mitochondrial permeability transition pore (mPTP) openings damage mitochondria, but transient mPTP openings protect against chronic cardiac stress. To probe the mechanism, we subjected isolated cardiac mitochondria to gradual Ca2+ loading, which, in the absence of BSA, induced long-lasting mPTP opening, causing matrix depolarization. However, with BSA present to mimic cytoplasmic fatty acid-binding proteins, the mitochondrial population remained polarized and functional, even after matrix Ca2+ release caused an extramitochondrial free [Ca2+] increase to >10 mu M, unless mPTP openings were inhibited. These findings could be explained by asynchronous transient mPTP openings allowing individual mitochondria to depolarize long enough to flush accumulated matrix Ca2+ and then to repolarize rapidly after pore closure. Because subsequent matrix Ca2+ reuptake via the Ca2+ uniporter is estimated to be > 100-fold slower than matrix Ca2+ release via mPTP, only a tiny fraction of mitochondria (