Minor contribution of NCX to Na-Ca exchange activity in brain mitochondria.

NCLX was identified as a mitochondrial Na-Ca exchanger. However, contribution of NCLX to overall mitochondrial Na-Ca exchange activity remains unclear, especially in brain mitochondria where plasma membrane Na-Ca exchanger NCX also exists. We studied the issue using isolated mouse brain mitochondria. The Na- as well as Li-dependent Ca efflux from mitochondria was significantly inhibited by a NCLX blocker, but was insensitive to NCX blockers, suggesting that NCLX comprises a major part in forward mode of mitochondrial Na-Ca exchange activity. On the other hand, the Na-dependent Ca influx into mitochondria, the reverse mode, was insensitive to all the blockers tested, suggesting unidentified Ca transport systems.