Integrating cytosolic calcium signals into mitochondrial metabolic responses - PubMed (original) (raw)

Integrating cytosolic calcium signals into mitochondrial metabolic responses

L D Robb-Gaspers et al. EMBO J. 1998.

Abstract

Stimulation of hepatocytes with vasopressin evokes increases in cytosolic free Ca2+ ([Ca2+]c) that are relayed into the mitochondria, where the resulting mitochondrial Ca2+ ([Ca2+]m) increase regulates intramitochondrial Ca2+-sensitive targets. To understand how mitochondria integrate the [Ca2+]c signals into a final metabolic response, we stimulated hepatocytes with high vasopressin doses that generate a sustained increase in [Ca2+]c. This elicited a synchronous, single spike of [Ca2+]m and consequent NAD(P)H formation, which could be related to changes in the activity state of pyruvate dehydrogenase (PDH) measured in parallel. The vasopressin-induced [Ca2+]m spike evoked a transient increase in NAD(P)H that persisted longer than the [Ca2+]m increase. In contrast, PDH activity increased biphasically, with an initial rapid phase accompanying the rise in [Ca2+]m, followed by a sustained secondary activation phase associated with a decline in cellular ATP. The decline of NAD(P)H in the face of elevated PDH activity occurred as a result of respiratory chain activation, which was also manifest in a calcium-dependent increase in the membrane potential and pH gradient components of the proton motive force (PMF). This is the first direct demonstration that Ca2+-mobilizing hormones increase the PMF in intact cells. Thus, Ca2+ plays an important role in signal transduction from cytosol to mitochondria, with a single [Ca2+]m spike evoking a complex series of changes to activate mitochondrial oxidative metabolism.

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References

    1. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12579-83 - PubMed
    1. J Biol Chem. 1994 Nov 4;269(44):27310-4 - PubMed
    1. J Bioenerg Biomembr. 1994 Oct;26(5):495-508 - PubMed
    1. J Biol Chem. 1995 Apr 7;270(14):8102-7 - PubMed
    1. J Biol Chem. 1995 Apr 28;270(17):9896-903 - PubMed

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