Genetic ablation of Immt induces a lethal disruption of the MICOS complex.

The mitochondrial contact site and cristae organizing system (MICOS) is important for crista junction formation and for maintaining inner mitochondrial membrane architecture. A key component of the MICOS complex is MIC60, which has been well studied in yeast and cell culture models. However, only one recent study has demonstrated the embryonic lethality of losing Immt (the gene encoding MIC60) expression. Tamoxifen-inducible ROSA-CreERT2-mediated deletion of Immt in adult mice disrupted the MICOS complex, increased mitochondria size, altered cristae morphology, and was lethal within 12 d. Pathologically, these mice displayed defective intestinal muscle function (paralytic ileus) culminating in dehydration. We also identified bone marrow (BM) hypocellularity in Immt-deleted mice, although BM transplants from wild-type mice did not improve survival. Altogether, this inducible mouse model demonstrates the importance of MIC60 in vivo, in both hematopoietic and non-hematopoietic tissues, and provides a valuable resource for future mechanistic investigations into the MICOS complex.

Simultaneous Writing and Erasing Using Probe Lithography Synchronized Erasing and Deposition (PLiSED).

Simultaneous writing and erasing of two and three molecules in one single step at the microscale using Polymeric Lithography Editor (PLE) probes is demonstrated. Simultaneous writing and erasing of three molecules was accomplished by rastering a nanoporous probe that was loaded with rhodamine B and fluorescein over a quinine-coated glass substrate. The solvated quinine molecules were erased and transported into the probe matrix, whereas both rhodamine and fluorescein molecules were simultaneously deposited and aligned with the path of the erased quinine on the substrate. The simultaneous writing and erasing of molecules is referred to as PLiSED. The writing and erasing speed can be easily tuned by adjusting the probe speed to as large as 10,000 µm2/s. The microscale patterns on the orders of square millimeter area were fabricated by erasing fluorescein with an efficiency (ηe) > 95% while simultaneously depositing rhodamine molecules at the erased spots. The roles of the probe porosity, transport medium, and kinetics of solvation for editing were also investigated─the presence of a transport medium at the probe-substrate interface is required for the transport of the molecules into and out of the probe. The physical and mechanical properties of the polymeric probes influenced molecular editing. Young's modulus values of the hydrated hydrogels composed of varying monomer/cross-linker ratios were estimated using atomic force microscopy. Probes with the highest observed erasing capacity were used for further experiments to investigate the effects of relative humidity and erasing time on editing. Careful control over experimental conditions provided high-quality editing of microscale patterns at high editing speed. Combining erasing and deposition of multiple molecules in one single step offers a unique opportunity to significantly improve the efficiency and the accuracy of lithographic editing at the microscale. PLiSED enables rapid on-site lithographic rectification and has considerable application values in high-quality lithography and solid surface modification.