Anatomy & Physiology
Volume 2 Issue 1 - 2016
Lipid Phosphate Phosphatase 3 LPP3 and Its Role in Mitochondrial Function
Mini Chandra1, Jonathan Fox1, Sumitra Miriyala1 and Manikandan Panchatcharam1*
Department of Cell biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, USA
Received: January 11, 2016 | Published: January 18, 2016
*Corresponding author: Manikandan Panchatcharam, Department of Cell biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, USA, Email:
Citation: Ghada AA (2015) Lipid Phosphate Phosphatase 3 LPP3 and Its Role in Mitochondrial Function. MOJ Anat Physiol 2(1): 00033. DOI: 10.15406/mojap.2016.02.00033


Lipid phosphate phosphatases (LPPs) are integral membrane proteins which are Mg2+ - independent and N-ethylmaleimide insensitive enzymes responsible for the dephosphorylation of lipid phosphates such as phosphatidic acid (PA), lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P) and diacylglycerol pyrophosphatase [1]. The mitochondrion is an active organelle which requires a constant source of phospholipids for homeostasis. The mitochondrial phospholipids such as phosphatidyl glycerol (PG) and phosphatidylethanolamine (PE) are synthesized in the mitochondrial membranes by Phosphatidic acid (PA) and lysophosphatidic acid (LPA) which are their precursors [2]. They are critical in controlling mitochondrial homeostasis [3] by influencing mitochondrial fusion [4], fission [5] and mitochondrial membrane proteins [6]. Organelles within a cell have contact sites to exchange metabolites and information in order to ensure cell survival [7]. Since the endoplasmic reticulum (ER) is a major source of lipid production in a cell, the ER and mitochondria communicate via contact sites known as the mitochondria-ER associated membranes (MAMs) [8]. This interface plays many roles in regulating the mitochondrial functioning [9] by the exchange of phospholipids between these two organelles [10], among which are the regulation of mitochondrial fusion [11], fission and lipid metabolism [12]. Thus mitochondria is dependent on the ER to provide phospholipids such as LPA and PA [13]. One of the main roles of lipid phosphates such as LPA, PA and Diacylglycerol (DAG) in the organelles is to maintain the cell membrane. The proper formation of cell membrane is essential for generating transport carriers involved in the transport of lipids and proteins from the Golgi apparatus to other sub cellular locations. The Golgi apparatus also houses the signaling and metabolic proteins. These transport carriers such as vesicles and tubules are generated in tightly regulated stages and the membrane deformation is prevented by many molecules which are proteins [14,15] and lipids controlling protein functions and altering the properties of the bilayer membrane [16,17]. Transport carriers are generated via the action of Phosphatidic acid phosphatases (PAPs) which dephosphorylates PA to produce DAG [18]. LPP is an isoform of Phosphatidic acid phosphatase (PAP) and plays an important role in the production of lipid signaling metabolites due to their function of dephosphorylation of lipid phosphates [19]. Among the mammalian isoforms of LPPs, the enzyme lipid phosphate phosphatase 3 (LPP3) is encoded in the gene PPAP2B in humans [20]. The importance of LPP3 is demonstrated in mice models where embryos with deficiency of LPP3 by inactivating Ppap2b result in embryonic lethality due to failure to develop an extra embryonic vasculature [21]. It is expressed mainly in the heart, lung and cerebellum [22]. In the organelle they are located in the plasma membrane [23] and end membrane namely the endoplasmic reticulum (ER), Golgi complex and endosomes [18]. In plasma membrane, their active catalytic site is located on the outside enabling them to interact with extracellular lipid phosphates. On the endomembrane it is located on the luminal side [24]. In addition to the above mentioned locations of LPP3, recently the presence of LPP3 in the ER-Golgi intermediate compartment (ERGIC), ER export sites (ERES) and Golgi complex has been demonstrated [25]. The results imply that LPP3 resides in the ER-Golgi intermediate compartment and constantly transports from the endoplasmic reticulum to the Golgi and vice versa. They determined the role of LPP3 in the functioning of the ERGIC by using propranolol which is an inhibitor of PAP [26] and suppressing LPP3 expression in HeLa cells. Propranolol treated cells showed less number of tubules and less motility in the ERGIC53-GFP expressing HeLa cells and the suppression of LPP3 exhibited decrease in LPP3 proteins. These results are an indication that LPP3 plays a role in the functioning and maintenance of ERGIC membrane. LPP3 is among the many enzymes which regulate membrane lipids in the secretory pathway [25,27-29]. It is responsible for the production of DAG by the dephosphorylation of PA both newly produced and the PA generated from the hydrolysis of Phosphatidylcholine (PC) [18]. LPP3 depletion is associated with the low levels of DAG. The same group also established the role of LPP3 in the formation of transport carriers in the Golgi [25]. They examined the Rab6-GFP transport tubules and vesicles, and the effect of both propranolol and LPP3 knockdown in Rab6-GFP expressing HeLa cells on their generation. The propranolol treated cells showed decreased rate of formation of Rab6-GFP transport carriers and the LPP3 depleted cells showed fewer tubules though they were longer than those found in control cells which may be due to the role of LPP3 in the fission of these tubules. The transport of proteins from Golgi back to the ER is dependent on the coatomer protein I (COPI) which is said to regulate the formation of retrograde transport carriers [30]. Rab6 is also known to play a role in the retrograde transport from Golgi to ER [31]. Therefore, The involvement of LPP3 in these transport mechanisms was studied [25] and the results indicated that LPP3 has a role in COPI dependent pathway as well as in the Rab6 dependent pathway. In addition to having a role in the transport mechanisms, LPP3 is also involved in the formation of transport carriers at the ERGIC and Golgi, in both these pathways. In conclusion, LPP3 takes part in the maintenance of the physical and functional component of mitochondria by playing a role in the transport of phospholipids from the ER to the mitochondria via both formations of transport carriers as well as mechanism of lipid exchange between the organelles.


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