Mitochondria transport and utilize iron for the synthesis of haem and Fe–S clusters. Although many proteins are known to be involved in these processes, additional proteins are likely to participate. To test this hypothesis, in the present study we used a genetic screen looking for yeast mutants that are synthetically lethal with the mitochondrial iron carriers Mrs3 and Mrs4. Several genes were identified, including an isolate mutated for Yfh1, the yeast frataxin homologue. All such triple mutants were complemented by increased expression of Rim2, another mitochondrial carrier protein. Rim2 overexpression was able to enhance haem and Fe–S cluster synthesis in wild-type or Δmrs3/Δmrs4 backgrounds. Conversely Rim2 depletion impaired haem and Fe–S cluster synthesis in wild-type or Δmrs3/Δmrs4 backgrounds, indicating a unique requirement for this mitochondrial transporter for these processes. Rim2 was previously shown to mediate pyrimidine exchange in and out of vesicles. In the present study we found that isolated mitochondria lacking Rim2 exhibited concordant iron defects and pyrimidine transport defects, although the connection between these two functions is not explained. When organellar membranes were ruptured to bypass iron transport, haem synthesis from added iron and porphyrin was still markedly deficient in Rim2-depleted mitochondrial lysate. The results indicate that Rim2 is a pyrimidine exchanger with an additional unique function in promoting mitochondrial iron utilization.
Skip Nav Destination
Article navigation
November 2011
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
October 27 2011
Rim2, a pyrimidine nucleotide exchanger, is needed for iron utilization in mitochondria
Heeyong Yoon;
Heeyong Yoon
*Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
Search for other works by this author on:
Yan Zhang;
Yan Zhang
*Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
Search for other works by this author on:
Jayashree Pain;
Jayashree Pain
†Department of Pharmacology and Physiology, UMDNJ, New Jersey Medical School, Newark, NJ 07101, U.S.A.
Search for other works by this author on:
Elise R. Lyver;
Elise R. Lyver
*Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
Search for other works by this author on:
Emmanuel Lesuisse;
Emmanuel Lesuisse
‡Laboratory of Mitochondria, Metals and Oxidative Stress, Institut Jacques Monod, CNRS-Université Paris Diderot, 7205, Paris Cedex 13, France
Search for other works by this author on:
Debkumar Pain;
Debkumar Pain
†Department of Pharmacology and Physiology, UMDNJ, New Jersey Medical School, Newark, NJ 07101, U.S.A.
Search for other works by this author on:
Andrew Dancis
Andrew Dancis
1
*Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
1To whom correspondence should be addressed (email adancis@mail.med.upenn.edu).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
June 10 2011
Revision Received:
July 18 2011
Accepted:
July 21 2011
Accepted Manuscript online:
July 21 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 440 (1): 137–146.
Article history
Received:
June 10 2011
Revision Received:
July 18 2011
Accepted:
July 21 2011
Accepted Manuscript online:
July 21 2011
Citation
Heeyong Yoon, Yan Zhang, Jayashree Pain, Elise R. Lyver, Emmanuel Lesuisse, Debkumar Pain, Andrew Dancis; Rim2, a pyrimidine nucleotide exchanger, is needed for iron utilization in mitochondria. Biochem J 15 November 2011; 440 (1): 137–146. doi: https://doi.org/10.1042/BJ20111036
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.