Biochemical and evolutionary aspects of anaerobically functioning mitochondria

Abstract

Mitochondria are usually considered to be the powerhouses of the cell and to be responsible for the aerobic production of ATP. However, many eukaryotic organisms are known to possess anaerobically functioning mitochondria, which differ significantly from classical aerobically functioning mitochondria. Recently, functional and phylogenetic studies on some enzymes involved clearly indicated an unexpected evolutionary relationship between these anaerobically functioning mitochondria and the classical aerobic type. Mitochondria evolved by an endosymbiotic event between an anaerobically functioning archaebacterial host and an aerobic alpha-proteobacterium. However, true anaerobically functioning mitochondria, such as found in parasitic helminths and some lower marine organisms, most likely did not originate directly from the pluripotent ancestral mitochondrion, but arose later in evolution from the aerobic type of mitochondria after these were already adapted to an aerobic way of life by losing their anaerobic capacities. This review will focus on some biochemical and evolutionary aspects of these fermentative mitochondria, with special attention to fumarate reductase, the synthesis of the rhodoquinone involved, and the enzymes involved in acetate production (acetate : succinate CoA-transferase and succinyl CoA-synthetase).

Identification and analysis of genes expressed in the adult filarial parasitic nematode Dirofilaria immitis

“…Together with this evidence, our observations argue for an alternative energy generation mechanism, relying heavily on the electron transfer complex I, in adult D. immitis. Interestingly, studies on the adult stages of the clade III pig intestine parasitic nematode Ascaris suum have revealed such an energy generation mechanism, the malate dismutation pathway or the PEPCK-succinate pathway, that requires the complexes I and II but not the others (Tielens and Van Hellemond, 1998;Kita and Takamiya, 2002;Tielens et al, 2002;van Hellemond et al, 2003). A developmental switch of energy generation occurs in A. suum at around stage L3, wherein an anaerobic electron transfer pathway in adults replaces the mammalian-type aerobic electron transfer in embryos and larvae.…”

Intermittent hypoxia leads to functional reorganization of mitochondria and affects cellular bioenergetics in marine molluscs

“…Anaerobic capacity was assessed by determining accumulation of anaerobic end products (L-alanine, succinate and acetate) (de Zwaan, 1991) and by measuring the enzyme activities at aerobic/anaerobic branchpoint -pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK) and malic enzyme (ME). In facultative anaerobes including molluscs, PK and PEPCK act as a metabolic switch, channeling glycolytic substrates to aerobic or anaerobic ATP production, respectively, and ME acts in concert with PEPCK diverting glycolytic substrates to anaerobic pathways (Zammit and Newsholme, 1978;van Hellemond et al, 2003). Therefore, a lower PK/PEPCK ratio and higher ME activity indicate activation of anaerobic pathways in molluscs (de Vooys, 1980;Sokolova and Pörtner, 2001;van Hellemond et al, 2003).…”

“…In facultative anaerobes including molluscs, PK and PEPCK act as a metabolic switch, channeling glycolytic substrates to aerobic or anaerobic ATP production, respectively, and ME acts in concert with PEPCK diverting glycolytic substrates to anaerobic pathways (Zammit and Newsholme, 1978;van Hellemond et al, 2003). Therefore, a lower PK/PEPCK ratio and higher ME activity indicate activation of anaerobic pathways in molluscs (de Vooys, 1980;Sokolova and Pörtner, 2001;van Hellemond et al, 2003). Energy status was assessed by tissue levels of adenylates and energy stores, as well as expression of a key cellular energy sensor, AMPactivated protein kinase (AMPKα) (Hardie, 2014).…”

Generation of adenosine tri-phosphate in Leishmania donovani amastigote forms

“…They are highly adapted for prolonged survival or even continuous functioning in the absence of oxygen, whereas many of them are adapted to alternating periods in the presence and absence of oxygen (Tielens and Van Hellemond 1998). Some anaerobically functioning eukaryotes, such as yeast and certain fishes, can survive without mitochondrial energy metabolism via cytosolic fermentations in which NADH/NADPH produced during glycolysis is consumed during the reduction of pyruvate to lactate or fumarate to succinate, which are subsequently excreted as end products (Van Hellemond et al 2003). It appeared from Table I that mitochondrial complex II electron transport inhibitor TTFA (IC 50 >4x10 3 µM) and Fo/F1-ATP synthase inhibitor oligomycin (IC 50 >200 µM) and DCCD (IC 50 >200 µM) were refractory to growth inhibition of amastigotes, whereas mitochondrial complex I and complex III inhibitors rotenone (IC 50 = 1.4 µM) and antimycin A (IC 50 = 0.8 µM) respectively, inhibited their growth significantly.…”