Mitochondrial F-ATP synthase as the permeability transition pore

The current state of research on the mitochondrial permeability transition pore (PTP) can be described in terms of three major problems: molecular identity, atomic structure and gating mechanism. In this review these three problems are discussed in the light of recent findings with special emphasis on the discovery that the PTP is mitochondrial F-ATP synthase (mtF_oF₁). Novel features of the mitochondrial F-ATP synthase emerging from the success of single particle cryo electron microscopy (cryo-EM) to determine F-ATP synthase structures are surveyed along with their possible involvement in pore formation. Also, current findings from the gap junction field concerning the involvement of lipids in channel closure are examined. Finally, an earlier proposal denoted as the 'Death Finger' is discussed as a working model for PTP gating.