Lipid signaling on the mitochondrial surface

Regulated production and elimination of the signaling lipids phosphatidic acid (PA), diacylglycerol (DAG), and phosphatidylinositol 4,5-bisphosphate (PI4,5P₂) creates a complex and interconnected signaling network that modulates a wide variety of eukaryotic cell biological events. PA production at the plasma membrane and on trafficking membrane organelles by classical Phospholipase D (PLD) through the hydrolysis of phosphatidylcholine (PC) has been studied widely. In this chapter, we review a newly identified, non-canonical member of the PLD superfamily, MitoPLD, which localizes to the mitochondrial surface and plays a role in mitochondrial fusion via the hydrolysis of cardiolipin (CL) to generate PA. The role of PA in facilitating the mitochondrial fusion event carried out by proteins known as Mitofusins is intriguing in light of the role classic PLD-generated PA plays in facilitating SNARE-mediated fusion of secretory membrane vesicles into the plasma membrane. In addition, however, PA on the mitochondrial surface may also trigger a signaling cascade that elevates DAG, leading to downstream events that affect mitochondrial fission and energy production. PA production on the mitochondrial surface may also stimulate local production of PI4,5P₂ to facilitate mitochondrial fission and subcellular trafficking or facilitate Ca²⁺ influx.