Mzm1 Influences a Labile Pool of Mitochondrial Zinc Important for Respiratory Function

Authors

Aaron Atkinson, University of Utah Health Sciences
Oleh Khalimonchuk, University of Nebraska-LincolnFollow
Pamela Smith, University of Utah Health Sciences Center
Hana Sabic, University of Utah Health Sciences Center
David Eide, University of Wisconsin-Madison
Dennis R. Winge, University of Utah Health Sciences Center

Document Type

Article

Date of this Version

2010

Citation

The Journal of Biological Chemistry, VOL. 285, NO. 25, pp. 19450–19459, June 18, 2010

Comments

© 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

Abstract

Zinc is essential for function of mitochondria as a cofactor for

several matrix zinc metalloproteins. We demonstrate that a

labile cationic zinc component of low molecular mass exists in

the yeast mitochondrial matrix. This zinc pool is homeostatically

regulated in response to the cellular zinc status. This pool

of zinc is functionally important because matrix targeting of a

cytosolic zinc-binding protein reduces the level of labile zinc

and interferes with mitochondrial respiratory function. We

identified a series of proteins that modulate the matrix zinc

pool, one of which is a novel conserved mitochondrial protein

designated Mzm1. Mutant mzm1∆ cells have reduced total and

labile mitochondrial zinc, and these cells are hypersensitive to

perturbations of the labile pool. In addition, mzm1∆ cells have a

destabilized cytochrome c reductase (Complex III) without any

effects on Complexes IV or V. Thus, we have established that a

link exists between Complex III integrity and the labile mitochondrial

zinc pool.