Editing Mitochondrion (section)

====Phospholipid transfer====
The MAM is enriched in enzymes involved in lipid biosynthesis, such as phosphatidylserine synthase on the ER face and phosphatidylserine decarboxylase on the mitochondrial face.<ref name="Vance-1996">{{cite journal | vauthors = Vance JE, Shiao YJ | title = Intracellular trafficking of phospholipids: import of phosphatidylserine into mitochondria | journal = Anticancer Research | volume = 16 | issue = 3B | pages = 1333–1339 | year = 1996 | pmid = 8694499 }}</ref><ref name="Lebiedzinska-2009">{{cite journal | vauthors = Lebiedzinska M, Szabadkai G, Jones AW, Duszynski J, Wieckowski MR | title = Interactions between the endoplasmic reticulum, mitochondria, plasma membrane and other subcellular organelles | journal = The International Journal of Biochemistry & Cell Biology | volume = 41 | issue = 10 | pages = 1805–1816 | date = October 2009 | pmid = 19703651 | doi = 10.1016/j.biocel.2009.02.017 }}</ref> Because mitochondria are dynamic organelles constantly undergoing [[mitochondrial fission|fission]] and [[mitochondrial fusion|fusion]] events, they require a constant and well-regulated supply of phospholipids for membrane integrity.<ref name="Twig-2008">{{cite journal | vauthors = Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, Las G, Alroy J, Wu M, Py BF, Yuan J, Deeney JT, Corkey BE, Shirihai OS | title = Fission and selective fusion govern mitochondrial segregation and elimination by autophagy | journal = The EMBO Journal | volume = 27 | issue = 2 | pages = 433–446 | date = January 2008 | pmid = 18200046 | pmc = 2234339 | doi = 10.1038/sj.emboj.7601963 }}</ref><ref name="Osman-2011">{{cite journal | vauthors = Osman C, Voelker DR, Langer T | title = Making heads or tails of phospholipids in mitochondria | journal = The Journal of Cell Biology | volume = 192 | issue = 1 | pages = 7–16 | date = January 2011 | pmid = 21220505 | pmc = 3019561 | doi = 10.1083/jcb.201006159 }}</ref> But mitochondria are not only a destination for the phospholipids they finish synthesis of; rather, this organelle also plays a role in inter-organelle trafficking of the intermediates and products of phospholipid biosynthetic pathways, ceramide and cholesterol metabolism, and glycosphingolipid anabolism.<ref name="Lebiedzinska-2009"/><ref name="Osman-2011"/>

Such trafficking capacity depends on the MAM, which has been shown to facilitate transfer of lipid intermediates between organelles.<ref name="Vance-1996"/> In contrast to the standard vesicular mechanism of lipid transfer, evidence indicates that the physical proximity of the ER and mitochondrial membranes at the MAM allows for lipid flipping between opposed bilayers.<ref name="Osman-2011"/> Despite this unusual and seemingly energetically unfavorable mechanism, such transport does not require ATP.<ref name="Osman-2011"/> Instead, in yeast, it has been shown to be dependent on a [[Protein complex|multiprotein]] tethering structure termed the ER-mitochondria encounter structure, or ERMES, although it remains unclear whether this structure directly mediates lipid transfer or is required to keep the membranes in sufficiently close proximity to lower the [[activation energy|energy barrier]] for [[lipid]] flipping.<ref name="Osman-2011"/><ref name="Kornmann-2009">{{cite journal | vauthors = Kornmann B, Currie E, Collins SR, Schuldiner M, Nunnari J, Weissman JS, Walter P | title = An ER-mitochondria tethering complex revealed by a synthetic biology screen | journal = Science | volume = 325 | issue = 5939 | pages = 477–481 | date = July 2009 | pmid = 19556461 | pmc = 2933203 | doi = 10.1126/science.1175088 | bibcode = 2009Sci...325..477K }}</ref>

The MAM may also be part of the secretory pathway, in addition to its role in intracellular lipid trafficking. In particular, the MAM appears to be an intermediate destination between the rough ER and the Golgi in the pathway that leads to [[very-low-density lipoprotein]], or VLDL, assembly and secretion.<ref name="Lebiedzinska-2009"/><ref name="Rusiñol-1994">{{cite journal | vauthors = Rusiñol AE, Cui Z, Chen MH, Vance JE | title = A unique mitochondria-associated membrane fraction from rat liver has a high capacity for lipid synthesis and contains pre-Golgi secretory proteins including nascent lipoproteins | journal = The Journal of Biological Chemistry | volume = 269 | issue = 44 | pages = 27494–27502 | date = November 1994 | pmid = 7961664 | doi = 10.1016/S0021-9258(18)47012-3 | doi-access = free }}</ref> The MAM thus serves as a critical metabolic and trafficking hub in lipid metabolism.