What it is
Oxidative phosphorylation (OXPHOS) is a key metabolic process that couples redox energy (released as electrons pass between molecules) to making ATP, the cell's energy currency. Some core subunits of the OXPHOS complexes are found across all domains of life, but many have diverged or expanded over evolution, as in the protozoan pathogen Acanthamoeba castellanii. Combining cryo-electron microscopy (imaging flash-frozen molecules to work out their structure) of unenriched mitochondrial lysate (broken-open mitochondria, with no complex purified first) with mass spectrometry proteomics (which identifies the proteins present), the authors resolved the structures of the organism's own mitochondrial ATP synthase (complex V), the chaperone Hsp60 and respiratory complex III. They captured the ATP synthase in a state inhibited by the protein IF1 and showed how subunits and extensions unique to Acanthamoeba stabilize it, including an extension of its β subunit that contacts the peripheral stalk (the arm that holds the enzyme's head in place). They also characterized an active dimer (a bound pair) of malate dehydrogenase, an enzyme of the tricarboxylic acid (TCA) cycle, built into that stalk.
Why it matters
In the protozoan Acanthamoeba, an active enzyme of the tricarboxylic acid cycle is built into ATP synthase, a direct protein tether between that cycle and ATP production. The structures also show how parts unique to Acanthamoeba stabilize its ATP synthase, an example of how OXPHOS machinery, partly shared across all domains of life, has diverged or expanded during evolution. The authors say the findings give structural insight into adaptations specific to this lineage that may tune protozoan metabolism.
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Filed underATP Synthase and ATPases Research, Enzyme Structure and Function, Mitochondrial Function and Pathology
