β barrel outer membrane proteins (β-OMPs) play vital roles in mitochondria, chloroplasts, and Gram-negative bacteria. Evolutionarily conserved complexes such as the mitochondrial sorting and assembly machinery (SAM) mediate the assembly of β-OMPs. We investigated the SAM-mediated assembly of the translocase of the outer membrane (TOM) core complex. Cryo–electron microscopy structures of SAM–fully folded Tom40 and the SAM-Tom40/Tom5/Tom6 complexes at ~3-angstrom resolution reveal that Sam37 stabilizes the mature Tom40 mainly through electrostatic interactions, thus facilitating subsequent TOM assembly. These results support the β barrel switching model and provide structural insights into the assembly and release of β barrel complexes.

Renal cell carcinoma (RCC) is a lethal genitourinary cancer and accounts 3% of total cancers worldwide. Various pleiotropic cytokines, i.e activator of signal transducer and activator of transcription 3 (STAT3), Cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (c-FLIP) and interleukin-6 (IL-6) could act to block the process of apoptosis in renal cancinoma cells, trigering its growth and proliferation. Their over-expression could activate several anti-apoptotic factors, hence it is important to block or down-regulate such factors in order to activate apoptosis in cancer cells. Up till now, several chemo and radiotherapies are being considered to combat renal carcinoma cells; however, there is a strong need to get some dietary therapeutic treatment. Hence, this study has used gastrointestinal digests of preserved eggs (GID-PE) for the apoptosis of Caki-1, ACHN and 786-O cells lines, in order to get insights about apoptosis in their mitochondrial pathway before and after treatment with (GID-PE). Moreover, changes in morphology accompanied by apoptosis analysis with different treatments have been carried out. Furthermore, ELISA analysis and mRNA expression of certain pro-inflammatory and anti-inflammatory cytokines were determined before and after treatment with GID-PE. Furthermore, the specific anti-apoptotic genes, i.e cFlip, Mcl-1, Bcl-XL and STAT3 were examined for their down-regulated expression after different treatments with GID-PE. Moreover, Bax expression acting as a pro-apoptotic gene was up-regulated up to some extent after treatments with GID-PE. Hence, GID-PE was confirmed to give anti-inflammatory effects in renal carcinoma cells could be used as health beneficial food product with anti-cancer properties.

AbstractMitochondria play vital functions in cellular metabolism, homeostasis, and apoptosis1-3. Most of the mitochondrial proteins are synthesized as precursors in the cytosol and imported into mitochondria for folding or maturation4,5. The translocase TIM22 complex is responsible for the import of multiple hydrophobic carrier proteins that are then folded in the inner membrane of mitochondria6-8. In mammalian cells, the TIM22 complex consists of at least six components, Tim22, Tim29, AGK, and three Tim chaperones (Tim9, Tim10a and Tim10b)9-14. Here, we report the cryo-EM structure of the human translocase TIM22 complex at an overall resolution of 3.7 angstrom. The core subunit, Tim22, contains four transmembrane helices, forming a partial pore that is open to the lipid bilayer. Tim29 is a single transmembrane protein that provides an N-terminal helix to stabilize Tim22 and a C-terminal intermembrane space (IMS) domain to connect AGK and two TIM chaperone hexamers to maintain complex integrity. One TIM hexamer comprises Tim9 and Tim10a in a 3:3 molar ratio, and the other consists of two Tim9 units, three Tim10a units, and one Tim10b unit. The latter hexamer faces the intramembrane region of Tim22, likely providing the dock to load the precursors to the partial pore of Tim22. Our structure serves as a molecular basis for the mechanistic understanding of TIM22 complex function.