Question

If the orientation of the mitochondrial ATP synthase were reversed so that the F1 unit were on the opposite side of the inner mitochondrial membrane, and assuming that nothing else is changed in the cell, what would be the consequences to the cell? Explain in details and use a diagram to support your answer

Answer 1

Mitochondria are the power houses of the cell. ATP synthase is an enzyme (molecular machine) catalyzing the reaction of ADP and Pi using proton gradient to produce the energy storage molecule ATP. In mitochondria ATP synthase is located in the inner membrane. ATP synthase is an F-ATPase consisting of two main subunits: F0 and F1. The hydrophilic catalytic F1 portion is sticking into matrix attached to cristae and is responsible for hydrolysing ATP.  Alpha and beta subunits of F1 makes hexamer with 6 binding sites, out which 3 are catalytically inactive binding to ADP. The other 3 subunits catalyse ATP synthesis. Gamma, delta and epsilon subunits are a part of rotational motor mechanism in which gamma subunit causes conformational changes (closed, half open and open states) of beta subunit. This allows binding of ATP and releasing once ATP is synthesized. F0 a hydrophobic region of ATP synthase is a proton pore which is embedded in the mitochondrial membrane. It consists of three main subunits a, b and c. Six c subunits make up the rotor ring and b subunit makes up the stalk which connects to F1. b subunit also prevents alpha-beta hexamer from rotating. Subunit a connects b subunit to c ring. The respiratory chain complexes pump protons across the matrix into intermembrane space thereby generating proton motive force that drives the ATP synthase. The pH of intermembrane space is low whereas the pH of matrix is high. The movement of proton across the matrix from intermembrane space through F0 subunit which drives the chemical reaction of ATP synthesis by F1 subunit in the matrix. Gmma subunit causes conformatiomational changes in beta subunit for synthesis of ATP molecules. If the ATP synthase enzyme is reversed such that F1 subunit is present at the other side of inner mitochondrial membrane i. e facing towards intermembrane space, there will be no ATP generation due to lack of proton motive force. The F0 subunit will be facing towards matrix and as there are no protons to be transported, there will be no proton motive force for driving ATP synthesis. The cell will be deprived of energy storage molecule i.e. ATP. The following diagram shows working of ATP synthase in normal conditions and also what happens when ATP synthase is reversed.