Publisher Summary This chapter describes the behavior of mitochondria in the living cell. The dynamics of mitochondria during fusion and fission and in intracellular displacement have important implications for understanding the supramolecular organization of cytoplasm. The physiological significance of the formation of mitochondrial reticula and the location of mitochondria close to energy-consuming structures is clear, and active locomotion establishes and maintains these important associations. Fusion and fission is of genetic significance, allowing the rapid exchange of alleles among different strands of DNA and thus accelerating the spreading of new mutations through a population of mitochondria. It also stabilizes the mitochondrial genome by facilitating recombinations and eliminating mutations. Fusion and fission of mitochondria also provide a structural control mechanism within the cell, allowing adaptation to varying energy demands during differentiation processes. A mitochondrial reticulum forms a pathway for energy transduction, which is equivalent to other transport systems such as cytoplasmic streaming or electrotonic signal transduction in some nerve cells. The role of supramolecular organization within the cytoplasm and the resulting microcompartmentation of the cell are necessary to elucidate these mechanisms.

Behavior of Mitochondria in the Living Cell

Tumor cells are characterized as rapidly dividing cells, and consequently they need a constant supply of both energy and nitrogen substrates. To resolve their energy requirements, they are able to use virtually any substrate: glucose [see 1 for a review; 2-4], lipids [5-7], ketone bodies [3], even amino acids [2-4, 8-10]. Nevertheless, the glucose and amino acid consumption by malignant tumor cells overcomes their own needs for their metabolic requirements; thus, tumor cells apparently waste glucose and amino acids without any profit [1, ll]. In this context, tumor has been described as a trap for glucose and nitrogen [12-13]. Tumors compete with the host for glucose [13-14]; this competence results in a progressive hypoglycemia [15] and host hepatic glycogen depletion [13]. In the same way, tumors compete for nitrogen compounds; this process produces in the host a negative nitrogen balance and a characteristic weight loss, and in the tumor a reciprocal nitrogen increase. The biochemical mechanisms underlying these phenomena still remain unclear. There is consensus that tumors increase protein degradation and reduce protein synthesis in the host tissues [16]. Alanine and glutamine are two efficient vehicles for the transport of nitrogen and carbon-skeletons between the different tissues in the living organism [17-18]. When a tumor develops, there is a net flux of amino acids from host tissues to the tumor [19]. Since ammonium ions are very toxic for most of the cells, glutamine is the physiological non-toxic ammonium vehicle between different mammalian tissues; therefore, glutamine is the main source of nitrogen for tumor cells [2, 20-21]. Thus, the presence of a tumor must produce great changes in the metabolism of glutamine in host tissues in such a way that host nitrogen metabolism is accomodated to tumor enhanced requirements of glutamine. To be used, glutamine must be transported into tumor mitochondria, where it is metabolized [21]. This implies two transport processes: the transport of glutamine across the plasma membrane and across the inner mitochondrial membrane. Once glutamine has been incorporated into tumor cells, this amino acid is quickly metabolized [12, 16, 19].

Relevance of glutamine metabolism to tumor cell growth.

Digitonin permeabilization does not affect mitochondrial function and allows the determination of the mitochondrial membrane potential of Trypanosoma cruzi in situ.

Yolanda Baquero

Papers

Measurement of 'in situ' mitochondrial membrane potential in Ehrlich ascites tumor cells during aerobic glycolysis.