Perspective: challenges and opportunities for the study of cardiolipin, a key player in bacterial cell structure and function.

Cardiolipin (CL) is a key player in bacterial cell biology. CL accumulates at the poles of rod-shaped cells; the polar localization and function of diverse bacterial proteins are CL-dependent. Cardiolipin (CL) is an unusual phospholipid comprised of a glycerol headgroup coupled with two phosphatidate moieties. CL-rich membrane domains are often visualized with the fluorescent indicator 10-N-nonyl-acridine orange (NAO). Recent data show that NAO can also indicate phosphatidylglycerol localization under different experimental conditions, in the absence of CL. The formation of CL-rich membrane domains at bacterial cell poles was predicted to occur spontaneously, by lipid microphase separation arising from the conical CL shape. New data reveal that membrane-anchored cardiolipin synthase A is targeted to the cytoplasmic membrane surface at bacterial cell poles. Thus, localized CL synthesis, interaction of CL with ClsA, and membrane curvature could all contribute to retention of CL at cell poles. These observations provide new insight regarding the mechanism for assembly of CL-rich membrane domains in prokaryotes and eukaryotes.