ERMES-mediated ER-mitochondria contacts: molecular hubs for the regulation of mitochondrial biology.
Organelles are separate yet interdependent units of eukaryotic cells. They provide an appropriate milieu for the catalysis of many biochemical reactions, and they must establish physical links to communicate and exchange metabolites throughout the cell. Interorganelle communication is an important, yet still poorly understood, aspect of cell biology. We recently identified a protein complex that we refer to as ERMES [endoplasmic reticulum (ER)-mitochondria encounter structure], the main function of which is to provide a tethering force between the ER and the mitochondria. This complex, composed of both ER and mitochondrial transmembrane proteins, is located at the interface of the two organelles and serves to zipper them together. Previous work had implicated several ERMES components in many different physiological processes. The identification of ERMES as an interorganelle tether allows us to re-examine the amply documented phenotypic consequences of the loss of this complex in the light of this new function, thus providing a unique opportunity to assess the physiological relevance of ER-mitochondria junctions. These phenotypes hint at a broad role for ER-mitochondria connections in regulating mitochondrial and cell physiology. In this Hypothesis, we speculate on the potential role of ER-mitochondria connections as hubs in regulating several aspects of mitochondrial biology, including the regulation of mitochondrial membrane biosynthesis, genome replication, Ca(2+) signaling and protein import. Finally, we discuss how cells might use ER-mitochondria communication to fine-tune these processes according to their metabolic needs.
Kornmann
Benoît
B
Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California at San Francisco, CA 94158, USA. benoit.kornmann@ucsf.edu
Walter
Peter
P
D000818:Animals; D020013:Calcium Signaling; D004261:DNA Replication / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D054629:Genome, Mitochondrial / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D021381:Protein Transport
D010743:Phospholipids
Nature. 2008 Dec 4;456(7222):605-10
19052620
Science. 2004 Apr 9;304(5668):253-7
15073369
Oncogene. 2008 Oct 27;27(50):6407-18
18955969
J Biol Chem. 1994 Nov 4;269(44):27494-502
7961664
J Cell Biol. 2009 Feb 23;184(4):583-96
19221197
Mol Cell. 2004 Oct 8;16(1):59-68
15469822
Physiol Rev. 2007 Jan;87(1):29-67
17237342
J Cell Biol. 2004 Oct 11;167(1):87-98
15479738
Science. 2009 Jul 24;325(5939):477-81
19556461
Sci STKE. 2004 Jan 13;2004(215):re1
14722345
Prog Lipid Res. 1997 Sep;36(2-3):103-30
9624424
Cell. 2009 Jan 9;136(1):163-74
19135897
Dev Cell. 2004 Jul;7(1):61-71
15239954
J Cell Biol. 2003 Nov 10;163(3):503-10
14597773
Mol Biol Cell. 2003 Nov;14(11):4618-27
13679517
J Biol Chem. 1990 May 5;265(13):7248-56
2332429
FASEB J. 2006 Feb;20(2):202-6
16449791
J Biol Chem. 2006 Aug 11;281(32):22819-26
16760475
J Bacteriol. 1971 Jul;107(1):377-81
5563875
Biochim Biophys Acta. 2009 Nov;1787(11):1309-16
19413950
EMBO J. 2005 Feb 23;24(4):717-29
15692567
Curr Opin Cell Biol. 2008 Aug;20(4):360-70
18490149
EMBO J. 2007 May 2;26(9):2229-39
17410204
J Cell Biol. 2006 Dec 18;175(6):901-11
17178908
Science. 1993 Oct 29;262(5134):744-7
8235595
Eur J Biochem. 1999 Sep;264(2):545-53
10491102
Prog Biophys Mol Biol. 1960;10:343-418
13742209
J Cell Biol. 2004 Mar 1;164(5):677-88
14981098
J Cell Biol. 2006 Sep 25;174(7):915-21
16982799
Biofactors. 1998;8(3-4):225-8
9914823
EMBO J. 1999 Sep 1;18(17):4733-43
10469652
J Cell Biol. 2001 Jan 22;152(2):401-10
11266455