Chapter 12 : The Mitochondrion

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This chapter provides an overview of the mitochondrion in malaria parasites in the light of what has been learned from the genome sequence. Historically, functions of the mitochondrion in malaria parasites were unclear because of its sac-like appearance and paucity of cristae. Prior to successful culture of , work on mitochondrial biochemistry also suffered from contamination with host components. The need to be aware of host mitochondrial contamination is still valid when using rodent malaria parasites as a source. Although mitochondria are called the powerhouse of cells for providing ATP, it is the generation of proton motive force across their inner membrane that justifies this moniker. Gene expression profiles of blood-stage parasites revealed an apparently coordinated expression of genes for the tricarboxylic acid (TCA) cycle enzymes. Mitochondrial ATP synthesis is carried out by a multiprotein rotary enzyme, FFATP synthase (complex V), located within the inner membrane by utilizing the proton motive force. The assembly of iron-sulfur [Fe-S] clusters is a complex process requiring participation of several enzymes, chaperones, and transporters. In metazoa, mitochondria are central to the process of programmed cell death or apoptosis, releasing several of proapoptotic molecules such as cytochrome in response to a number of different apoptotic signals, including the collapse of mitochondrial membrane potential. DNA replication, recombination, and repair would require participation of a large number of proteins in these complex processes. Mitochondrial translation machinery is necessary for the synthesis of three proteins encoded by mitochondrial DNA (mtDNA).

Citation: Vaidya A. 2005. The Mitochondrion, p 234-252. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch12

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DNA Polymerase I
DNA Polymerase gamma
Dihydrofolate Reductase Inhibitors
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Image of FIGURE 1

An outline of mitochondrial processes in malaria parasites. An outer membrane with a putative porin would allow molecules up to 1,500 daltons to freely diffuse to and from the intermembrane space. Transporters in the outer and inner membrane that assist mitochondrial import of proteins are not shown, nor are metabolite transporters located in the inner membrane. Major metabolic processes described in the text are shown in black boxes, and the flow of substrates and metabolites is indicated by arrows. The orientation of the dehydrogenases is assumed from biochemical studies of . Glycerol 3-phosphate dehydrogenase is not shown, but is likely to face the intermembrane space.

Citation: Vaidya A. 2005. The Mitochondrion, p 234-252. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch12
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Image of FIGURE 2

A description of the Q cycle through which ubiquinol is oxidized and protons are translocated at the cytochrome complex. Bifurcation of electrons from QH at the Q site is a key feature of the Q cycle. Sites at which cytochrome inhibitors work are indicated at the right. See the text for a description.

Citation: Vaidya A. 2005. The Mitochondrion, p 234-252. In Sherman I (ed), Molecular Approaches to Malaria. ASM Press, Washington, DC. doi: 10.1128/9781555817558.ch12
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