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PDZD8 is not the 'functional ortholog' of Mmm1, it is a paralog

Jeremy G Wideman1,2, Dario L Balacco3, Tim Fieblinger2,4

  • 1Department of Biosciences, University of Exeter, Exeter, EX4 4QD, UK.

F1000Research
|August 16, 2018
PubMed

Insights

PDZD8 tethers mitochondria to the ER in mammals, similar to fungal ERMES. However, PDZD8 is a paralog, not an ortholog, of yeast Mmm1, revealing a complex evolutionary history of ER-mitochondria tethering.

Area of Science:

  • Cell Biology
  • Evolutionary Biology
  • Genetics

Background:

  • The ER-mitochondria encounter structure (ERMES) complex in fungi tethers mitochondria to the endoplasmic reticulum (ER).
  • PDZD8 (PDZ domain containing 8) has been identified as a protein that tethers mitochondria to the ER in mammalian cells.
  • The functional similarity suggests PDZD8 might be an ortholog of the yeast Mmm1 (maintenance of mitochondrial morphology protein 1) protein.

Purpose of the Study:

  • To investigate the evolutionary relationship between PDZD8 and Mmm1.
  • To clarify the phylogenetic status of PDZD8 in relation to ER-mitochondria tethering mechanisms.
  • To understand the evolutionary history of ER-mitochondria tethering in animals and fungi.

Main Methods:

  • Phylogenetic analyses were conducted to compare PDZD8 and Mmm1 across different species.
  • Gene co-occurrence patterns were analyzed in lineages related to animals and fungi.
  • Identification of related paralogs of PDZD8 in various fungal and animal-related lineages.

Main Results:

  • Phylogenetic data indicate that PDZD8 and Mmm1 are paralogs, not orthologs.
  • PDZD8 co-occurs with ERMES components in animal-related lineages, supporting its paralog status.
  • Two additional PDZD8 paralogs were identified: one in flagellated fungi and another in unicellular animal relatives.

Conclusions:

  • The identification of PDZD8 as a paralog of Mmm1 necessitates a re-evaluation of the evolution of ER-mitochondria tethering.
  • The evolutionary history of ER-mitochondria tethering is complex, involving gene duplication, gain, and loss events.
  • These findings provide insights into the diversification of organelle contact sites across eukaryotes.
Keywords:
ERMESPdz8evolutionorthologparalog

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