An unexpected consequence of the COVID-19 pandemic has been the realization of how the modern supply-and-demand economy influences our everyday life. Supply chain issues and shortages of common household items like toilet paper are being felt on a global scale like never in recent memory. Like in the macroscopic world, individual cells must also manage supply chains among their organelles and adjust them to their current needs, a topic of major research focus in many labs. A study from Jean Vance initiated the mechanistic dissection of how one such inter-organelle supply chain — phospholipid exchange between the endoplasmic reticulum (ER) and mitochondria — is orchestrated.

The paper is noteworthy because it demonstrated that following biochemical fractionation, a fraction of mitochondria co-purified with the ER network. Importantly, this so-called mitochondria-associated membrane (MAM) sample exhibited remarkable enzymatic properties: it could efficiently convert phosphatidylserine (PS), which is generated in the ER, to phosphatidylethanolamine (PE), made within mitochondria. Isolated mitochondria were not capable of this step-wise synthesis. This indicated that the MAM fraction (referred to as fraction X) contained reconstituted junctions between the two organelles that enabled lipid exchange and the synthesis of PE from PS, thereby demonstrating the important role of inter-organelle communication in glycerophospholipid metabolism.

Published in 1990 as a single-author article, the study represents a milestone in understanding inter-organelle crosstalk. Pioneering work from George Palade and others had visualized ER–mitochondria contact sites with electron microscopy, but the cellular roles for these junctions remained generally underexplored. Vance’s biochemical work beautifully complements the microscopy-based approaches of Palade. Together, these studies are a prime example of the emergence of modern cell biology as a discipline blending microscopy and biochemical approaches to dissect inter-organelle communication.

Today, many studies reveal inter-organelle contacts as conduits for lipid and metabolite exchange

Today, many studies reveal inter-organelle contacts as conduits for lipid and metabolite exchange, indicating that these membrane contact sites serve as versatile metabolic synthesis platforms. As we try to deal with the supply chain issues in our modern human world, we need to look no further than within our cells to understand that life is constantly challenged with the issue of delivering supplies efficiently across space and time.