Phosphatidic Acid (PA)-preferring Phospholipase A1 Regulates Mitochondrial Dynamics

Abstract

Background: Phosphatidic acid (PA) is involved in membrane dynamics. Results: PA-preferring phospholipase A 1 (PA-PLA 1 ) affects mitochondrial morphology in an activity-dependent manner. Gene disruption of PA-PLA 1 in mice causes sperm malformation due to mitochondrial organization defects. Conclusion: PA-PLA 1 regulates mitochondrial dynamics. Significance: We demonstrate an in vivo function of PA-PLA 1 and suggest a possible mechanism of PA regulation of the mitochondrial membrane.

Unlocking ATP13A2/PARK9 activity

“…The cellular functions of PI (3,5)P2 might partially relate to ATP13A2, since loss of ATP13A2 results in neurodegeneration, an increased lysosomal pH and impaired autophagy. 2 We further show that ATP13A2 mediates protection against rotenone-induced mitochondrial stress requiring both catalytic activity of ATP13A2 and the lipids PA and PI (3,5)P2. This hints to a lipiddependent activation of ATP13A2 that is important for mitochondrial homeostasis and/or clearance 2 (Fig.…”

“…1). In fact, we show that the signaling lipids phosphatidic acid (PA) and phosphatidylinositol (3,5)bisphosphate (PI(3,5)P2) interact with the N-terminal region. Biochemical evidence further indicated that ATP13A2 may reside in an inactive autophosphorylated state and that both lipids stimulate catalytic autophosphorylation, suggesting that the lipids unlock ATP13A2 activity.…”

“…In fact, PA and PI(3,5)P2 may be markers of stress regulating mitochondrial fragmentation and clearance. The levels of PA control mitochondrial fragmentation and elongation, 3 and suppressed by the phosphatase Ptpmt1 under basal conditions, PI(3,5)P2 increases under mitochondrial dysfunction, which induces mitochondrial fragmentation. 4 Together, PA and PI(3,5)P2 are important for endo-/lysosomal membrane dynamics and mitochondrial homeostasis, suggesting that ATP13A2 might be implicated in vesicular transport, fusion or fission events that are coupled to mitochondrial homeostasis.…”

“…PI(3,5)P2-deficiency in mice carrying mutations in Vac14, an activator of PIKFYVE, a lipid kinase which generates PI(3,5)P2 from PI(3)P, also results in neurodegeneration. PI (3,5) P2 regulates endo-/lysosome morphology, acidification, trafficking, membrane fusion/fission events and is implicated in autophagy. The cellular functions of PI (3,5)P2 might partially relate to ATP13A2, since loss of ATP13A2 results in neurodegeneration, an increased lysosomal pH and impaired autophagy.…”

Acute exposure to an electric field induces changes in human plasma lysophosphatidylcholine (lysoPC)-22:4 levels: Molecular insight into the docking of lysoPC-22:4 interaction with TRPV2

“…Comprehensive analysis of phospholipids was conducted in essentially the same manner as described previously [28][29]. Briefly, total phospholipids were extracted from the plasma with the Bligh-Dyer method [30].…”