Calcium and mitochondria

Abstract

The literature suggests that the physiological functions for which mitochondria sequester Ca(2+) are (1). to stimulate and control the rate of oxidative phosphorylation, (2). to induce the mitochondrial permeability transition (MPT) and perhaps apoptotic cell death, and (3). to modify the shape of cytosolic Ca(2+) pulses or transients. There is strong evidence that intramitochondrial Ca(2+) controls both the rate of ATP production by oxidative phosphorylation and induction of the MPT. Since the results of these processes are so divergent, the signals inducing them must not be ambiguous. Furthermore, as pointed out by Balaban [J. Mol. Cell. Cardiol. 34 (2002 ) 11259-11271], for any repetitive physiological process dependent on intramitochondrial free Ca(2+) concentration ([Ca(2+)](m)), a kind of intramitochondrial homeostasis must exist so that Ca(2+) influx during the pulse is matched by Ca(2+) efflux during the period between pulses to avoid either Ca(2+) buildup or depletion. In addition, mitochondrial Ca(2+) transport modifies both spatial and temporal aspects of cytosolic Ca(2+) signaling. Here, we look at the amounts of Ca(2+) necessary to mediate the functions of mitochondrial Ca(2+) transport and at the mechanisms of transport themselves in order to set up a hypothesis about how the mechanisms carry out their roles. The emphasis here is on isolated mitochondria and on general mitochondrial properties in order to focus on how mitochondria alone may function to fulfill their physiological roles even though the interactions of mitochondria with other organelles, particularly with endoplasmic and sarcoplasmic reticulum [Sci. STKE re1 (2004) 1-9], may also influence this story.

Regulation of Ca2+ signalling and Ca2+-mediated cell death by the transcriptional coactivator PGC-1α

“…Mitochondria are organized in a complex interconnected network all over the cell interior, and thus are able to form contacts with the different sources of Ca 2 þ (for recent reviews see Rizzuto et al 2 and Parekh 3 ). These close contacts ensure the uptake of Ca 2 þ into the mitochondrial matrix, leading to three important consequences: (i) mitochondria function as cellular Ca 2 þ buffers, shaping the global cellular Ca 2 þ response; 4 (ii) Ca 2 þ entering into the mitochondrial matrix regulates mitochondrial metabolism; 5 (iii) the extent of mitochondrial Ca 2 þ load is a key determinant of the intrinsic apoptotic pathway, thus controlling cell fate under physiological and pathological conditions. 6 The composite Ca 2 þ uptake system of the mitochondrial membranes comprises the voltage-dependent anion channel of the outer membrane and the Ca 2 þ uniporter (mitochondrial Ca 2 þ uniporter (MCU)) in the inner membrane.…”

Activity-dependent Increases in Local Oxygen Consumption Correlate with Postsynaptic Currents in the Mouse CerebellumIn Vivo

“…In comparison, less is known regarding the local in vivo control of the cerebral metabolic rate of O 2 (CMRO 2 ), as most knowledge of mitochondrial function was obtained from isolated mitochondria, dissociated cell cultures, or brain slices (Kann and Kovács, 2007). CMRO 2 is controlled by the ADP/ATP ratio, as well as by changes in the mitochondrial Ca 2ϩ concentration that stimulate the activity of tricarboxylic acid (TCA) cycle dehydrogenases and central enzymes in the respiratory chain (Gunter et al, 2004). In addition, respiration is controlled by the Ca 2ϩ -dependent mitochondrial aspartate-glutamate transporter, which increases mitochondrial nicotinamide adenine dinucleotide (NADH) levels (Satrú stegui et al, 2007).…”

Letm1, the mitochondrial Ca 2+ /H + antiporter, is essential for normal glucose metabolism and alters brain function in Wolf–Hirschhorn syndrome

“…Because the MCU's V max is orders of magnitude higher than that of Ca 2+ mito exchange mechanisms, repetitive high Ca 2+ cyto elevations trigger Ca 2+ mito overload and can lead to the mitochondrial permeability transition (9,10). Free [Ca 2+ ] mito in intact cells usually fluctuates below the micromolar range, suggesting that Ca 2+ exchangers are crucial for maintaining Ca 2+ mito homeostasis at low Ca 2+ cyto levels to preserve mitochondrial homeostasis and bioenergetics.…”