Where the endoplasmic reticulum and the mitochondrion tie the knot: the mitochondria-associated membrane (MAM)

Biochimica Et Biophysica Acta
Arun Raturi, Thomas Simmen

Abstract

More than a billion years ago, bacterial precursors of mitochondria became endosymbionts in what we call eukaryotic cells today. The true significance of the word "endosymbiont" has only become clear to cell biologists with the discovery that the endoplasmic reticulum (ER) superorganelle dedicates a special domain for the metabolic interaction with mitochondria. This domain, identified in all eukaryotic cell systems from yeast to man and called the mitochondria-associated membrane (MAM), has a distinct proteome, specific tethers on the cytosolic face and regulatory proteins in the ER lumen of the ER. The MAM has distinct biochemical properties and appears as ER tubules closely apposed to mitochondria on electron micrographs. The functions of the MAM range from lipid metabolism and calcium signaling to inflammasome formation. Consistent with these functions, the MAM is enriched in lipid metabolism enzymes and calcium handling proteins. During cellular stress situations, like an altered cellular redox state, the MAM alters its set of regulatory proteins and thus alters MAM functions. Notably, this set prominently comprises ER chaperones and oxidoreductases that connect protein synthesis and folding inside the ER to mitochondrial ...Continue Reading

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