Sharing the wealth: The versatility of proteins targeted to peroxisomes and other organelles

Abstract

Peroxisomes are eukaryotic organelles with critical functions in cellular energy and lipid metabolism. Depending on the organism, cell type, and developmental stage, they are involved in numerous other metabolic and regulatory pathways. Many peroxisomal functions require factors also relevant to other cellular compartments. Here, we review proteins shared by peroxisomes and at least one different site within the cell. We discuss the mechanisms to achieve dual targeting, their regulation, and functional consequences. Characterization of dual targeting is fundamental to understand how peroxisomes are integrated into the metabolic and regulatory circuits of eukaryotic cells.

Mpf1 is a novel factor that affects the dual distribution of tail-anchored proteins between mitochondria and peroxisomes

“…Considering the number of shared proteins between mitochondria and peroxisomes and the de novo formation of peroxisomes via mitochondria-derived vesicles (at least in mammalian cells), several studies speculate that peroxisomes evolved to facilitate the quality control of mitochondria under periods of stress and to relieve mitochondria from the burden of hosting oxidation enzymes of the β-oxidation pathway (Bittner et al, 2022b; Speijer, 2017). This symbiotic relationship between mitochondria and peroxisomes might have allowed peroxisomes to utilize several mitochondrial proteins for their own needs like those proteins involved in fission (Fis1) and quality control (Msp1).…”

“…Moreover, mitochondria contribute indirectly to the targeting of the phosphatase Ptc5p to peroxisomes via a mitochondrial transit. These cross-talks are proposed to eventually lead to targeting of these proteins to both organelles when peroxisomes became autonomous over time (Bittner et al, 2022b; Stehlik et al, 2020). Distribution of the dually localized TA protein Fis1 to mitochondria and peroxisomes is aided by Pex19 (Cichocki et al, 2018).…”

“…While a clear mechanism for targeting TA proteins to the secretory pathway has been worked out (Schuldiner et al, 2008; Stefanovic & Hegde, 2007), the mechanism involved in the correct targeting of TA proteins to mitochondria is still widely unknown. It has been previously shown that optimal hydrophobicity of the transmembrane domain and the presence of charged residues is essential for the correct targeting of TA proteins to mitochondria and/or peroxisomes (Bittner et al, 2022a; Borgese et al, 2007; Costello et al, 2017). While the mitochondrial import (MIM) complex was suggested to promote the biogenesis of the TA proteins Fis1 and Gem1 (Doan et al, 2020), other studies have also reported insertion of Fis1 to the mitochondrial outer membrane (MOM) and to lipid vesicles in an unassisted manner (Krumpe et al, 2012, Vitali et al, 2020).…”

TheHansenula polymorphaMitochondrial Carrier Family proteins Mir1 and Aac2 are dually localized at peroxisomes and mitochondria

“…An increasing number of proteins are identified to dually localize on mitochondria and peroxisomes. Initially, this mainly included peroxisomal matrix enzymes (e.g., Cat2 or Ptc5, (Elgersma et al, 1995) (Stehlik et al, 2020) (Bittner et al, 2022)and tail anchored proteins, which localize to the mitochondrial outer membrane and the peroxisomal membrane (e.g., yeast Fis1 and Gem1 (Cichocki et al, 2018).…”

The RNA world of fungal pathogens

“…Significantly, stop-codon readthrough stands out as the predominant mechanism employed by both fungi and mammals to generate cryptic peroxisomal targeting sequences, whereby ribosomes continue translating past a termination codon to produce peroxisomal isoforms. This low rate of stop-codon readthrough rates enables the release of small but steady amounts of these enzymes to support peroxisome metabolism [21,22]. For translational readthrough, both U. maydis and human cells require a specific sequence context involving the UGA stop codon followed by the dinucleotide CU [23].…”