© Borgis - New Medicine 2/2004, s. 34-36
Pathology of mitochondria. Structural and functional aspects*
Department of Cell Biology and Molecular Pathology (chaired by Department of Medical Chemistry), Medical University of Gdańsk, Gdańsk, Poland
The present article overviews the structural and functional aspects of mitochondria under physiological and pathological conditions. Structure and function of mitochondria, and morfological changes in various conditions are described. The authors point out several problems to be solved in the future.
Recent advance in cellular and molecular biology has added a body of new information to the structure and function of mitochondria. It has turned out that mitochondria play a central role in the initiation of apoptosis. Mitochondria are endowed with several key components that control apoptotic processes: Bcl-2 family genes, cytochrome c and apoptosis inducing factor (AIF). Application of fluorescent dyes to cell biology has made it possible to detect the membrane potential of mitochondria (DYm) in situ. Data have accumulated that the cytoskeletons are intimately associated with mitochondria and that the size and spatial distribution of mitochondria in the cell are controlled by microtubules and microfilaments. Furthermore, several genes controlling the size and distribution of mitochondria in the cell have been identified (1). Extensive studies have been also made on the mechanism and pathophysiological meaning of the phenomenon of the megamitochondria (MG) formation, most distinct morphological changes of mitochondria induced under various pathological conditions (2). Data have accumulated to demonstrate that free radicals are intimately related to the mechanism of MG formation (2).
The present article overviews the structural and functional aspects of mitochondria under physiological and pathological conditions.
STRUCTURE OF MITOCHONDRIA UNDER PHYSIOLOGICAL CONDITIONS
It had been believed for a long time that mitochondria were granular in their shapes measuring 1-2mm in diameter and were separated from each other in the cell. However, the reconstitution of three-dimensional structure of mitochondria using serial-sectioning technique for electron microscopy of yeast cells revealed that mitochondria were connected to each other making one huge megamitochondrion (MG) (3). Similar techniques were applied to various tissues including those of mammals, and it turned out mitochondria were connected to each other far more frequently than expected on one plane of section for electron microscopy. Existence of MG in mammals has been proved in several different tissues or cells: sperm, diaphragm skeletal muscles, liver (related to aging) and adrenal (2). Application of fluorescent dyes to cell biology has also demonstrated that mitochondria are highly filamentous rather than granular in the cell under physiological conditions. It has been reported that 1-7 MG exist in Saccharomyces cervisiae when they are cultured in the presence of sucrose while 25-100 smaller mitochondria are detected in the cell, while one huge, branched mitochondrion was detected when they are cultured in the presence of lactate or glycerol (4). MGs were detected in the liver tissue of bats during hibernation (5). It could be deduced from these data that when energy requirement of the cell is high mitochondria became smaller by fission increasing their number thus increasing their surface areas. There may be more chance for mitochondria to obtain materials from endoplasmic reticulum. On the other hand, when energy requirement of the cell is relatively low, mitochondria coalesce by fusion making MG. I will discuss functional aspects of MG later.
FUNCTION OF MITOCHONDRIA UNDER PHYSIOLOGICAL CONDITIONS
Function of mitochondria can be classified into two groups: those common to mitochondria possibly regardless of their sources of tissues, and those specific for mitochondria in certain tissues. Major functions belonging to the first entity include ATP synthesis, Ca2+ homeostasis and the control of apoptosis. Functions belonging to the second entity include steroidogenesis in mitochondria of adrenal cortex, ovary, testis an placenta; heat production in brown fat mitochondria; and heme synthesis in mitochondria of erythroblasts in bone marrow. Here, I will refer briefly only to the role of mitochondria in apoptotic processes.
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