Ceramide and the mitochondrial respiratory chain

Ceramide is a group of sphingolipids found in cell membranes, composed of a sphingoid base linked to a fatty acid of varying chain length. Initially regarded as purely structural components, this group of molecules is now recognized as a key signaling and regulatory elements in cell biology. Ceramide species differing in acyl chain length, with distinct biophysical properties, execute distinct functions and effects. Some of these modulate mitochondrial function and oxidative phosphorylation (OXPHOS). Certain ceramides were associated with decreased mitochondrial respiratory chain (MRC) activity, increased reactive oxygen species (ROS) production and oxidative stress, mitochondrial outer membrane permeabilization (MOMP), reduced mitochondrial membrane potential, mitophagy and apoptosis. In this review we aim to summarize the most relevant findings linking ceramide to mitochondria. The physiological significance of synthetic short and naturally occurring long chain ceramides in modulating mitochondrial function with emphasis on the MRC will be discussed.