Premium
A histidine‐rich motif mediates mitochondrial localization of ZnT2 to modulate mitochondrial function
Author(s) -
Seo Young Ah,
Kelleher Shan L
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.228.1
Subject(s) - mitochondrion , microbiology and biotechnology , mitochondrial biogenesis , biology , mitochondrial carrier , biochemistry , mitochondrial fusion , oxidative phosphorylation , inner mitochondrial membrane , chemistry , mitochondrial dna , gene , bacterial outer membrane , escherichia coli
Mitochondrial Zinc (Zn) pools have emerged as a central player in regulating bioenergetics and apoptosis. However, mechanisms through which Zn is imported into mitochondria have yet to be identified. Herein, we documented that the Zn transporter ZnT2 was associated with the inner mitochondrial membrane and acts as an auxiliary Zn importer into mitochondria in mammary cells. We found that attenuation of ZnT2 expression significantly reduced mitochondrial Zn uptake (−20%) and total mitochondrial Zn pools (−20%). A ZnT2‐HA fusion protein localized to mitochondria significantly increased Zn uptake (+38%) and mitochondrial Zn pools (+23%), directly implicating ZnT2 in mitochondria Zn import. Confocal microscopy with ZnT2‐GFP fusion proteins of point mutations in the N‐terminus revealed a histidine‐rich motif ( 51 HH X H 54 ) that is important for mitochondrial targeting of ZnT2. More importantly, the expansion of mitochondrial Zn pools by ZnT2 over‐expression significantly reduced ATP biogenesis (−25%) and mitochondrial oxidation (−56%) concurrent with increased apoptosis, confirming a functional role for ZnT2‐mediated Zn import into mitochondria. These results identify the first Zn transporter directly associated with mitochondria and suggest that the mammary gland requires novel mechanisms to modulate mitochondria‐specific functions. Grant Funding Source: National Institute of Health