Therapeutic Modulation of Apoptosis: Targeting the BCL-2 Family at the Interface of the Mitochondrial Membrane

A vast portion of human disease results when the process of apoptosis is defective. Disorders resulting from inappropriate cell death range from autoimmune and neurodegenerative conditions to heart disease. Conversely, prevention of apoptosis is the hallmark of cancer and confounds the efficacy of cancer therapeutics. In the search for optimal targets that would enable the control of apoptosis, members of the BCL-2 family of anti- and pro-apoptotic factors have figured prominently. Development of BCL-2 antisense approaches, small molecules, and BH3 peptidomimetics has met with both success and failure. Success-because BCL-2 proteins play essential roles in apoptosis. Failure-because single targets for drug development have limited scope. By examining the activity of the BCL-2 proteins in relation to the mitochondrial landscape and drawing attention to the significant mitochondrial membrane alterations that ensue during apoptosis, we demonstrate the need for a broader based multi-disciplinary approach for the design of novel apoptosis-modulating compounds in the treatment of human disease

Cryo-electron microscopy of phospholipid suspensions

Authors have used cryo-electron microscopy to examine the influence of temperature on the morphology of phospholipid vesicles. This technique involves plunging a thin film of an aqueous suspension into a liquid cryogen which is cooled to its melting point by liquid nitrogen. For initial studies, they chose the synthetic phospholipid dimyristoylphosphatidycholine (DMPC, T=297K, T*=302K) to study the thermotropic phase transitions. To investigate the influence of temperature on the morphology of DMPC vesicles, high resolution images were taken at different temperatures, at constant defocus

Image formation modeling in cryo-electron microscopy

Microscopic imaging and technolog