In “The Enigmatic Membrane” (The Scientist, February 1, 2012), Muriel Mari, Sharon A. Tooze, and Fulvio Reggiori report, “Despite years of research, the longstanding mystery of where the autophagosome gets its double lipid bilayers is not much clearer.” The autophagosome is a device inside a cell that chemically incinerates dead stuff, clutter and germs, producing fuel:
Cells live longer than their internal components. To keep their cytoplasm clear of excess or damaged organelles, as well as invading pathogens, or to feed themselves in time of nutrient deprivation, cells degrade these unwanted or potentially harmful structures, and produce needed food and fuel, using a process they have honed over millions of years. Known as autophagy, this catabolic process involves the selection and the sequestration of the targeted structures into unique transport vesicles called autophagosomes, which then deliver the contents to lysosomes where they are degraded by lytic enzymes. This conserved eukaryotic pathway plays a central role in a multitude of physiological processes, including programmed cell death, development, and differentiation.
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Despite significant advances over the last 20 years in the understanding of how this process works and what purposes it serves, there is a lingering question—how are autophagosomes formed? More specifically, where do their not one, but two lipid bilayers come from? Autophagosomes are not pre-built organelles that become active upon the induction of autophagy; they are made from scratch each time a cell needs to degrade one or more of its contents. And they are giant vesicles, with an average diameter of approximately 700–800 nanometers, which can further expand to accommodate large structures such as cellular organelles and bacteria, and which are made in large quantities under autophagy-inducing conditions. As a result, progression of autophagy requires a ready supply of lipids. This aspect of the process has intrigued researchers since the discovery of autophagy in the 1950s and ’60s. Understanding the biogenesis of autophagosomes will provide information about how cells generate new compartments in response to internal and external cues, and will thus lead to a clearer conception of cell homeostasis.
And much more.
The authors look at various possible sources of the essential membrane without much success. This looks like a promising area for design theorists. Especially because many diseases (“cardiovascular and autoimmune diseases, neuro- and myodegenerative disorders, and malignancies”) are linked to problems with cleaning up the cell. If we knew how the autophagosomes suddenly get made from scratch as needed, we might have a better idea how to make it happen more quickly or more often- when nature needs a nudge.