Regulation of ATP production by mitochondrial Ca(2+)

Abstract

Stimulation of mitochondrial oxidative metabolism by Ca(2+) is now generally recognised as important for the control of cellular ATP homeostasis. Here, we review the mechanisms through which Ca(2+) regulates mitochondrial ATP synthesis. We focus on cardiac myocytes and pancreatic β-cells, where tight control of this process is likely to play an important role in the response to rapid changes in workload and to nutrient stimulation, respectively. We also describe a novel approach for imaging the Ca(2+)-dependent regulation of ATP levels dynamically in single cells.

Fig. 1

Role of Ca²⁺ uptake by mitochondria in the heart.

Fig. 2

Potential role of Ca²⁺ uptake by mitochondria in the pancreatic β-cell. ETC, electron transport chain. See the text for further details of the Ca²⁺ sensitive intramitochondrial dehydrogenases.

Fig. 3

Principle of simultaneous patch-clamp recording and multiparameter imaging of compartmentalised Ca²⁺ and ATP/ADP in single cells.

Fig. 4

Mitochondrial Ca²⁺ (A) and [ATP/ADP]_cyt (B) increases respond to the frequency of electrical bursting and Ca²⁺ oscillations in a single primary mouse β-cell. Depolarisations of the plasma membrane were applied at different frequency from 10 min⁻¹ to 1 min⁻¹.

Fig. 5

Multiphasic increases in [ATP/ADP]_c are prompted by high glucose in the β-cell. Recordings and image collection were as in Fig. 4; note the second phase of ATP/ADP increase ∼400 s after the increase in glucose .