Biochemistry, Department of


Date of this Version



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


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


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.