Abstract
The control of mitochondrial function is a cardinal issue in the field of cardiac bioenergetics, and the analysis of mitochondrial regulations is central to basic research and in the diagnosis of many diseases. Interaction between cytoskeletal proteins and mitochondria can actively participate in mitochondrial regulation. Potential candidates for the key roles in this regulation are the cytoskeletal proteins plectin and tubulin. Analysis of cardiac cells has revealed regular arrangement of β-tubulin II, fully co-localized with mitochondria. β-Tubulin IV demonstrated a characteristic staining of branched network, β-tubulin III was matched with Z-lines, and β-tubulin I was diffusely spotted and fragmentary polymerized. In contrast, HL-1 cells were characterized by the complete absence of β-tubulin II. Comparative analysis of cardiomyocytes and HL-1 cells revealed a dramatic difference in the mechanisms of mitochondrial regulation. In the heart, colocalization of β-tubulin isotype II with mitochondria suggests that it can participate in the coupling of ATP-ADP translocase (ANT), mitochondrial creatine kinase (MtCK), and VDAC (ANT-MtCK-VDAC). This mitochondrial supercomplex is responsible for the efficient intracellular energy transfer via the phosphocreatine pathway. Existing data suggest that cytoskeletal proteins may control the VDAC, contributing to maintenance of mitochondrial and cellular physiology.
Highlights
THE ROLE OF CYTOSKELETON IN THE REGULATION OF MITOCHONDRIAL RESPIRATORY FUNCTION High requirements for energy supply in oxidative muscles are met by aerobic oxidation of fatty acids and glucose coupled to ATP production in mitochondria
It has been shown that the decrease in mitochondrial affinity for exogenous ADP in permeabilized cardiac cells is related to the local restrictions on ADP diffusion in cardiac cells, including limitation of the permeability of the voltage-dependent anion channel (VDAC) known as porin in the mitochondrial outer membrane (MOM) (Figure 1B) (Saks et al, 1993, 1995; Kuznetsov et al, 1996; Milner et al, 2000; Appaix et al, 2003; Rostovtseva and Bezrukov, 2008; Rostovtseva et al, 2008)
The striking difference between both morphology, arrangement, and ADP kinetics in adult cardiomyocytes and HL-1 cells suggests the importance of specific mitochondrial organization controlled by cytoskeletal proteins (Anmann et al, 2006)
Summary
THE ROLE OF CYTOSKELETON IN THE REGULATION OF MITOCHONDRIAL RESPIRATORY FUNCTION High requirements for energy supply in oxidative muscles are met by aerobic oxidation of fatty acids and glucose coupled to ATP production in mitochondria. Studies of permeabilized cells and muscle fibers have shown very different kinetics of ATP synthesis (remarkably increased apparent Km for ADP in the regulation of mitochondrial respiration) in comparison to isolated mitochondria (Belikova et al, 1990; Saks et al, 1991a, 1993).
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