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.

PubMed Disclaimer

Cited by

Regulation of the mitochondrial proton gradient by cytosolic Ca²⁺ signals.
Poburko D, Demaurex N. Poburko D, et al. Pflugers Arch. 2012 Jul;464(1):19-26. doi: 10.1007/s00424-012-1106-y. Epub 2012 Apr 24. Pflugers Arch. 2012. PMID: 22526460 Review.
Sarcolipin Is a Key Determinant of the Basal Metabolic Rate, and Its Overexpression Enhances Energy Expenditure and Resistance against Diet-induced Obesity.
Maurya SK, Bal NC, Sopariwala DH, Pant M, Rowland LA, Shaikh SA, Periasamy M. Maurya SK, et al. J Biol Chem. 2015 Apr 24;290(17):10840-9. doi: 10.1074/jbc.M115.636878. Epub 2015 Feb 24. J Biol Chem. 2015. PMID: 25713078 Free PMC article.
Mitochondrial priming modifies Ca2+ oscillations and insulin secretion in pancreatic islets.
Ainscow EK, Rutter GA. Ainscow EK, et al. Biochem J. 2001 Jan 15;353(Pt 2):175-80. doi: 10.1042/0264-6021:3530175. Biochem J. 2001. PMID: 11139378 Free PMC article.
Mitochondrial memory banks. Calcium stores keep a record of neuronal stimulation.
Kaczmarek LK. Kaczmarek LK. J Gen Physiol. 2000 Mar;115(3):347-50. doi: 10.1085/jgp.115.3.347. J Gen Physiol. 2000. PMID: 10694262 Free PMC article. Review. No abstract available.

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

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