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Published online 19 February 2001. doi:10.1083/jcb.152.4.683
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© The Rockefeller University Press, 0021-9525/2001//683 $5.00
The Journal of Cell Biology, Volume 152, Number 4, , 2001 683-692


Original Article

Connection of the Mitochondrial Outer and Inner Membranes by Fzo1 Is Critical for Organellar Fusion



Stefan Fritza, Doron Rapaportb, Elisabeth Klannera, Walter Neuperta, and Benedikt Westermanna

a Institut für Physiologische Chemie, Universität München, 80336 München, Germany
b Department of Biochemistry, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel
Institut für Physiologische Chemie, Universität München, Goethestrasse 33, 80336 München Germany.49-89-5996-27049-89-5996-265

benedikt.westermann{at}bio.med.uni-muenchen.de

Mitochondrial membrane fusion is a process essential for the maintenance of the structural integrity of the organelle. Since mitochondria are bounded by a double membrane, they face the challenge of fusing four membranes in a coordinated manner. We provide evidence that this is achieved by coupling of the mitochondrial outer and inner membranes by the mitochondrial fusion machinery. Fzo1, the first known mediator of mitochondrial fusion, spans the outer membrane twice, exposing a short loop to the intermembrane space. The presence of the intermembrane space segment is required for the localization of Fzo1 in sites of tight contact between the mitochondrial outer and inner membranes. Mutations in the intermembrane space domain of yeast Fzo1 relieve the association with the inner membrane. This results in a loss of function of the protein in vivo. We propose that the mitochondrial fusion machinery forms membrane contact sites that mediate mitochondrial fusion. A fusion machinery that is in contact with both mitochondrial membranes appears to be functionally important for coordinated fusion of four mitochondrial membranes.

Key Words: Fzo1 • membrane contact sites • membrane fusion • mitochondria • organelle inheritance



© 2001 The Rockefeller University Press

Abbreviations used in this paper: AAC, ADP/ATP carrier; DHFR, dihydrofolate reductase; 5-FOA, 5-fluoro-orotic acid; GFP, green fluorescent protein; mtGFP, mitochondria-targeted GFP; YPD, yeast extract–peptone-dextrose; YPG, yeast extract–peptone-glycerol.



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