Mitochondrial ATP synthase c-subunit leak channel triggers cell death upon loss of its F1 subcomplex.

Mitochondrial ATP synthase is vital not only for cellular energy production but also for energy dissipation and cell death. ATP synthase c-ring was suggested to house the leak channel of mitochondrial permeability transition (mPT), which activates during excitotoxic ischemic insult. In this present study, we purified human c-ring from both eukaryotic and prokaryotic hosts to biophysically characterize its channel activity. We show that purified c-ring forms a large multi-conductance, voltage-gated ion channel that is inhibited by the addition of ATP synthase F1 subcomplex. In contrast, dissociation of F1 from FO occurs during excitotoxic neuronal death suggesting that the F1 constitutes the gate of the channel. mPT is known to dissipate the osmotic gradient across the inner membrane during cell death. We show that ATP synthase c-subunit knock down (KD) prevents the osmotic change in response to high calcium and eliminates large conductance, Ca2+ and CsA sensitive channel activity of mPT. These findings elucidate the gating mechanism of the ATP synthase c-subunit leak channel (ACLC) and suggest how ACLC opening is regulated by cell stress in a CypD-dependent manner.

Phylogenetic relationships of Chlamydomyces, Harzia, Olpitrichum, and their sexual allies, Melanospora and Sphaerodes.

Phylogenetic analyses using internal transcribed spacer (ITS), large subunit rRNA (LSU), and small subunit (SSU) sequence data showed that Harzia, Chlamydomyces, and Olpitrichum are con-generic. Thus, Chlamydomyces, and Olpitrichum were reduced to synonymy of Harzia. The generic concept was amended and expanded accordingly. Eight new combinations were proposed. Melanospora and Sphaerodes are phylogenetically related to Harzia. However, several members of Melanospora and Sphaerodes are polyphyletic and belong to Hypocreales or Microascales in Sordariomycetes. The Proteophiala morph is not only a crucial morphological character, but also has a phylogenetical significance in defining Melanosporales. It is hypothesized that the taxa with synanamorphic or asexual Proteophiala all belong to Ceratostomataceae, Melanosporales.