8 - Physiology of Mitochondria

Abstract

This chapter discusses the physiology of mitochondria. It is mentioned that the complex of enzymes that couples substrate oxidation to adenosine triphosphate (ATP) synthesis is located in mitochondria, The chapter discusses several concepts related to the physiological setting of mitochondria—namely, chemiosmotic theory, factors of respiration rate in cells, factors of the rate of ATP synthesis in cells, ion leaks in mitochondria, mitochondrial proton cycle and the uncoupling proteins, anion exchange carriers, mitochondrial calcium cycle, mitochondrial potassium cycle, physiological role of MitOK ATP in heart, MitOK ATP as the end effector of protection, against ischemia-reperfusion injury, mitochondrial permeability transition (MPT), and mitochondrial involvement in apoptosis. Mitochondria have their own unique physiology, which is directed toward maintenance of vesicular integrity and proper functioning in energy transduction. The setting in which this physiology takes place is explained by the elegant postulates of the chemiosmotic theory. The very high electrical membrane potential required for ATP synthesis is stated to have particular importance. The internal aqueous compartment of mitochondria, called the matrix , contains the enzymes of the Krebs tricarboxylic acid cycle. The matrix is enclosed by a highly folded, insulating membrane called the inner membrane , and this structure is separated from the cytosol by a more permeable outer membrane. The electrical driving force causes significant inward leak of protons, which dissipates energy and reduces the efficiency of oxidative phosphorylation. The high membrane potential also drives significant diffusive uptake of K + across the membrane, resulting in osmotic swelling of the matrix and threatening the vesicular integrity of the organelle. The high driving force for K + uptake has also been exploited to drive K + inward through the highly regulated K ATP channel. Mitochondria have exploited the high membrane potential to drive Ca 2+ rapidly, both inward, via the Ca 2+ channel, and outward, via the Na + - Ca 2+ antiporter. The mitochondrial Ca 2+ cycle, thus, allows oscillatory cytosolic Ca 2+ signals to be transmitted to the matrix, where the high frequency of oscillations causes sustained activation of enzymes that synthesize NADH, a major substrate for the electron transport chain. The great resurgence of interest in mitochondrial physiology is because of the realization that mitochondria play a more central role in pathophysiology than previously thought. The apoptotic pathway is activated by cytochrome “c” and other proteins released from the intermembrane space. The new uncoupling proteins are thought to participate in the pathways that regulate body weight.