PKCs pick through Ca2

杨柳

Calcium signals destined for mitochondria are first screened by protein kinase C (PKC) isoforms, according to Pinton et al., on page 223. Different PKCs then adjust the organelles' responses to their liking.* t, T- q/ o" p% M! b) g

% v8 q$ S  H* d2 i6 M' n0 C9 W' oPKC is a Ca2 -activated kinase that comes in many flavors. Pinton et al. analyzed the contribution of several of these flavors to Ca2  signaling by overexpressing or inhibiting individual isoforms in cells. Their effects were assessed by stimulating cells with an extracellular agonist to elicit Ca2  stores from the ER into the cytoplasm.
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5 e' M1 {& h6 }/ e, w' yOne flavor, PKC, limited all Ca2  signaling by dampening this ER release. Others, however, worked specifically at the mitochondria. PKC increased mitochondrial Ca2  uptake, whereas PKC? and  reduced it. Thus, activation of PKC upon initial stimulation may alter the effect of subsequent Ca2  spikes. Mitochondria are known to respond less to the second of two consecutive stimuli. The authors now show that PKC? is needed for this dampening. This function might make cells less sensitive to apoptotic signals, for example, which induce mitochondrial Ca2  influx.3 d8 g- v" @; Q1 s7 F5 z* v
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The PKC isoforms that decrease Ca2  uptake also decrease mitochondrial membrane potential. There may be a causal link, but mitochondrial Ca2  transporters have not been cloned, so identifying the relevant PKC substrates will require the purification of mitochondrial proteins that are phosphorylated in response to Ca2 .(Mitochondrial desensitization to the sec)