Andrey V Kuznetsov
Innsbruck Medical University, Austria
Title: Cytoskeleton and regulation of mitochondrial function: The role of beta-tubulin II and plectin
Biography
Biography: Andrey V Kuznetsov
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 with cardiac phenotype 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 and VDAC. This mitochondrial supercomplex is responsible for the efficient intracellular energy transfer via the phosphocreatine pathway. We found also that in skeletal muscle of plectin knockout mice, mitochondrial content was reduced; mitochondria were aggregated in sarcoplasmic and subsarcolemmal regions, and were no longer associated with Z-disks. Our results show that the depletion of distinct plectin isoforms (P1b and P1d) affects mitochondrial network organization and function in different ways. Existing data suggest that cytoskeletal proteins may control the VDAC, contributing to the regulation of mitochondrial and cellular physiology.
References:
1. Bagur R, Tanguy S, Foriel S, Grichine A, Sanchez C, Pernet-Gallay K, Kaambre T, Kuznetsov AV, Usson Y, Boucher F, Guzun R. (2016) The impact of cardiac ischemia/reperfusion on the mitochondria-cytoskeleton interactions. Biochim. Biophys. Acta. 1862(6):1159-71.
2. Winter L, Kuznetsov AV, Grimm M, Zeöld A, Fischer I, Wiche G. (2015) Plectin isoform P1b and P1d deficiencies differentially affect mitochondrial morphology and function in skeletal muscle. Human Molecular Genetics. 24(16):4530-44.
3. Kuznetsov AV, Javadov S, Sickinger S, Frotschnig S, Grimm M. (2014) H9c2 and HL-1 cells demonstrate distinct features of energy metabolism, mitochondrial function and sensitivity to hypoxia-reoxygenation. Biochim. Biophys. Acta. 1853(2):276-284.
4. Varikmaa M, Bagur R, Kaambre T, Grichine A, Timohhina N, Tepp K, Shevchuk I, Chekulayev V, Metsis M, Boucher F, Saks V, Kuznetsov AV, Guzun R. (2014) Role of mitochondria-cytoskeleton interactions in respiration regulation and mitochondrial organization in striated muscles. Biochim. Biophys. Acta. 1837(2):232-45.
5. Tepp K, Mado K, Varikmaa M, Klepinin A, Timohhina N, Shevchuk I, Chekulayev V, Kuznetsov AV, Guzun R, Kaambre T. (2014) The role of tubulin in the mitochondrial metabolism and arrangement in muscle cells. J. Bioenerg. Biomembr. 46:421-434.
6. Javadov S, Kuznetsov AV. (2013) Mitochondria: the cell powerhouse and nexus of stress. Frontiers in Physiology. Vol. 4, article 207.
7. Kuznetsov AV, Javadov S, Guzun R, Grimm M, Saks VA. (2013) Cytoskeleton and regulation of mitochondrial function: the role of beta-tubulin II. Frontiers in Physiology. Vol. 4, article 82.