Archived Comments for:
Evolution of vacuolar proton pyrophosphatase domains and volutin granules: clues into the early evolutionary origin of the acidocalcisome
This article posits in the discussion that acidocalcisomes could have been used as a source of energy polyphosphate to drive the V-PPase and create a proton motive force in the LUCA. This is not possible. In modern organisms, the V-PPase has the intracellular region of the protein, which hydrolyses PPi, facing the cytoplasm. The extracellular region faces the vacuole/acidocalcisome/extracellular medium, into which H+/Na+ are pumped, thus acidifying it. That gradient is then available in principle for use by a similarly-oriented ATPase to synthesise ATP from ADP+Pi, which is the authors' hypothesis. This _requires_ that the PPi is on the intracellular side - which it isn't in the acidocalcisome. Alternatively, if the V-PPase were turned around to face the lumen side of the acidocalcisome, it would be pumping protons _out_ into the cytoplasm, thus acidifying and killing the cell! So, though I am completely comfortable with the idea that V-PPases are ancient enzymes, the posited role of V-PPase in energy metabolism in this paper can not be true.
In addition, the structure of two V-PPases were solved after this paper was written, and it is _completely_ clear that polyphosphate is not a viable substrate. It would protrude out of the hydrolytic centre, preventing closure and thus preventing pumping.
Error in logic in article
26 January 2015
This article posits in the discussion that acidocalcisomes could have been used as a source of energy polyphosphate to drive the V-PPase and create a proton motive force in the LUCA. This is not possible. In modern organisms, the V-PPase has the intracellular region of the protein, which hydrolyses PPi, facing the cytoplasm. The extracellular region faces the vacuole/acidocalcisome/extracellular medium, into which H+/Na+ are pumped, thus acidifying it. That gradient is then available in principle for use by a similarly-oriented ATPase to synthesise ATP from ADP+Pi, which is the authors' hypothesis. This _requires_ that the PPi is on the intracellular side - which it isn't in the acidocalcisome. Alternatively, if the V-PPase were turned around to face the lumen side of the acidocalcisome, it would be pumping protons _out_ into the cytoplasm, thus acidifying and killing the cell! So, though I am completely comfortable with the idea that V-PPases are ancient enzymes, the posited role of V-PPase in energy metabolism in this paper can not be true.
In addition, the structure of two V-PPases were solved after this paper was written, and it is _completely_ clear that polyphosphate is not a viable substrate. It would protrude out of the hydrolytic centre, preventing closure and thus preventing pumping.
Competing interests
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