May 12, 2014 - ATP synthesis in podocytes is then examined; as the kidney ... processes involved with mitochondrial dysfunction and podocyte injury required ...
Cell Biology and Pathology of Podocytes Liu Z-H, He JC (eds): Podocytopathy. Contrib Nephrol. Basel, Karger, 2014, vol 183, pp 64–82 DOI: 10.1159/000359929
Role of Mitochondria in Podocyte Injury Yanggang Yuan a · Songming Huang b, c · Aihua Zhang b, c
a Department
of Nephrology, The First Affiliated Hospital of Nanjing Medical University, b Department of Nephrology, Nanjing Children’s Hospital, Affiliated to Nanjing Medical University, and c Institute of Pediatrics, Nanjing Medical University, Nanjing, PR China
Abstract
Mitochondria are important cell organelles. Often described as the ‘powerhouses’ of cells, mitochondria are responsible for the synthesis of adenosine triphosphate (ATP) and the supply of energy to cells. They also participate in many other biological functions in cells, such as the generation of reactive oxygen species (ROS), intracellular signaling, and regulation of cell apoptosis. Recent medical advances have provided further insights into the roles of mitochondrial dysfunction in a variety of human diseases, such as diabetes, neurodegenerative diseases, septic shock,
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Mitochondria are cellular organelles that produce the energy required for cellular processes through synthesis of adenosine triphosphate (ATP). They also contribute to a wide range of cellular functions, including reactive oxygen species (ROS) generation, calcium homeostasis, and induction of apoptosis. Mitochondria also contain their own DNA, known as mitochondrial DNA (mtDNA). Through these varied roles, mitochondria are important in heredity, growth, metabolism, and the occurrence and progression of diseases. Podocytes are highly specialized epithelial cells of the kidney. Podocyte injury is considered a key factor in the development of many forms of glomerular disease. A description of the structure and functions of mitochondria is provided, before focusing on mitochondrial dysfunction in podocyte injury. Changes in mtDNA are discussed, using focal segmental glomerulosclerosis as an example of a nuclear-encoded mitochondrial disease. ATP synthesis in podocytes is then examined; as the kidney consumes a large amount of energy, any disruption in supply is likely to cause renal dysfunction. Mitochondrial ROS production and calcium disorders, and mitophagy and mitochondrial dynamics are also discussed. Finally, an outline of the numerous challenges in understanding the biological processes involved with mitochondrial dysfunction and podocyte injury required to de© 2014 S. Karger AG, Basel velop strategies for improving human health is provided.
cardiomyopathy, coronary artery diseases, age-related degenerative diseases, primary biliary cirrhosis, and hepatitis C. In particular, mitochondrial dysfunction plays key roles in the physiology and pathophysiology of podocyte injury.
Biology of Mitochondria
Structures A mitochondrion comprises four functional parts (from outer to inner): outer mitochondrial membrane (OMM), intermembrane space, inner mitochondrial membrane (IMM), and mitochondrial matrix [2, 4]. The OMM is a smooth unit membrane enclosing the mitochondrion. With a structure similar to eukaryotic cell membranes, the OMM functions as the barrier between the mitochondrion and the cytoplasm. It contains a large number of integral proteins, called porins. These proteins form 2–3 nm wide channels that are permeable to molecules