The Outer Mitochondrial Membrane, a Smooth 'Coat' with Many Holes and Many Roles: Preparation, Protein Components, Interactions with Other Membranes, Involvement in Health, Disease, and as a Drug Target

Mitochondria were first isolated near the middle (1948) of the past century, visualized shortly thereafter by electron microscopy, and each mitochondrion was shown to consist of four major compartments: (1) an outer membrane (the subject of this article), (2) an inner membrane, (3) an intermembrane space located between the two membranes, and (4) a matrix, soluble space surrounded by the inner membrane. As ATP synthesis (oxidative phosphorylation) was shown to be associated with the inner membrane, the outer membrane drew little attention for many years and was not subjected to serious analysis until the late 1960s. Meticulous and very difficult work resulted in the separation of mitochondria into four distinct fractions, each representing one of its four major compartments, and this article focuses on the outer mitochondrial membrane summarizing its preparation, characterization, and roles in cellular life and death and its impact on health and disease.