Fumarase: A paradigm of dual targeting and dual localized functions

Ohad Yogev, Adi Naamati, Ophry Pines*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

82 Scopus citations

Abstract

The enzyme fumarase is a conserved protein in all organisms with regard to its sequence, structure and function. This enzyme participates in the tricarboxylic acid cycle in mitochondria which is essential for cellular respiration in eukaryotes. However, a common theme conserved from yeast to humans is the existence of a cytosolic form of fumarase; hence this protein is dual localized. We have coined identical (or nearly identical) proteins situated in different subcellular locations 'echoforms' or 'echoproteins'. Fumarase was the first example of a dual localized protein whose mechanism of distribution was found to be based on a single translation product. Consequently, fumarase has become a paradigm for three unique eukaryotic cellular phenomena related to protein dual localization: (a) distribution between mitochondria and the cytoplasm involves reverse translocation; (b) targeting to mitochondria involves translation coupled import; and (c) there are two echoforms possessing distinct functions in the respective subcellular compartments. Here we describe and discuss these fumarase related phenomena and in addition point out approaches for studying dual function of distributed proteins, in particular compartment-specific depletion. In the case of fumarase, the cytoplasmic function was only recently discovered; the enzyme was found to participate in the cellular response to DNA double strand breaks. Strikingly, upon DNA damage the protein is transported from the cytosol to the nucleus, where by virtue of its enzymatic activity it participates in the DNA damage response. The enzyme fumarase is a conserved protein in all eukaryotes with regard to its sequence, structure, function and dual localization to mitochondria and the cytosol. Here we discuss fumarase as a paradigm for mechanisms by which proteins are dual targeted to different subcellular compartments and how such identical proteins (termed 'echoforms') can perform the distinct functions in the different compartments

Original languageAmerican English
Pages (from-to)4230-4242
Number of pages13
JournalFEBS Journal
Volume278
Issue number22
DOIs
StatePublished - Nov 2011

Keywords

  • bimodal targeting
  • dual targeting
  • echoforms/echoproteins
  • fumarase/fumarate hydratase
  • mitochondria

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