Rim2, a pyrimidine nucleotide exchanger, is needed for iron utilization in mitochondria

Heeyong Yoon1, Yan Zhang, Jayashree Pain

  • 1Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA.

Insights

Mitochondrial protein Rim2 is essential for iron utilization, impacting haem and Fe-S cluster synthesis. This study reveals Rim2

Area of Science:

  • Mitochondrial biology
  • Cellular iron metabolism
  • Protein function

Background:

  • Mitochondria are crucial for iron metabolism, essential for synthesizing haem and iron-sulfur (Fe-S) clusters.
  • While known proteins are involved, the full complement of proteins regulating mitochondrial iron transport remains incompletely understood.

Purpose of the Study:

  • To identify novel proteins involved in mitochondrial iron transport and utilization.
  • To investigate the role of the mitochondrial carrier protein Rim2 in iron homeostasis and related metabolic pathways.

Main Methods:

  • Utilized a genetic screen in yeast to identify mutants synthetically lethal with mitochondrial iron carriers Mrs3 and Mrs4.
  • Analyzed the effects of Rim2 overexpression and depletion on haem and Fe-S cluster synthesis.
  • Assessed mitochondrial iron and pyrimidine transport defects in Rim2-deficient mitochondria.

Main Results:

  • Identified several genes, including Yfh1 (yeast frataxin homologue), as essential for viability when mitochondrial iron carriers Mrs3 and Mrs4 are absent.
  • Rim2 overexpression rescued synthetic lethality and enhanced haem and Fe-S cluster synthesis.
  • Rim2 depletion impaired haem and Fe-S cluster synthesis and caused mitochondrial iron and pyrimidine transport defects.

Conclusions:

  • Rim2 plays a unique and essential role in promoting mitochondrial iron utilization, beyond its known function in pyrimidine exchange.
  • Mitochondrial iron transport and pyrimidine transport may be interconnected through Rim2.
  • Rim2 is critical for efficient haem and Fe-S cluster biogenesis.

Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
Riboswitches01:56

Riboswitches

Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
Ribosomal RNA Synthesis02:53

Ribosomal RNA Synthesis

Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Ribosomal RNA Synthesis02:53

Ribosomal RNA Synthesis

Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Microbes and Other Elemental Cycles01:24

Microbes and Other Elemental Cycles

Microbial activity plays a pivotal role in the biogeochemical cycling of iron and manganese, especially at the redox gradients characteristic of stratified aquatic environments. These cycles are driven by microbial transformations between oxidized and reduced forms of the metals, allowing organisms to exploit them for metabolic energy and structural purposes.Iron Cycling Across Redox GradientsIn neutral, oxygen-rich surface waters, iron is predominantly found in its oxidized, insoluble ferric...