Insights into the Structure and Function of the Pex1/Pex6 AAA-ATPase in Peroxisome Homeostasis

Cells. 2022 Jun 29;11(13):2067. doi: 10.3390/cells11132067.

Abstract

The AAA-ATPases Pex1 and Pex6 are required for the formation and maintenance of peroxisomes, membrane-bound organelles that harbor enzymes for specialized metabolism. Together, Pex1 and Pex6 form a heterohexameric AAA-ATPase capable of unfolding substrate proteins via processive threading through a central pore. Here, we review the proposed roles for Pex1/Pex6 in peroxisome biogenesis and degradation, discussing how the unfolding of potential substrates contributes to peroxisome homeostasis. We also consider how advances in cryo-EM, computational structure prediction, and mechanisms of related ATPases are improving our understanding of how Pex1/Pex6 converts ATP hydrolysis into mechanical force. Since mutations in PEX1 and PEX6 cause the majority of known cases of peroxisome biogenesis disorders such as Zellweger syndrome, insights into Pex1/Pex6 structure and function are important for understanding peroxisomes in human health and disease.

Keywords: AAA-ATPase; PEX1; PEX26; PEX6; organelle biogenesis; peroxisomes; translocation.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / metabolism
  • Adenosine Triphosphatases / metabolism
  • Homeostasis
  • Humans
  • Membrane Proteins* / metabolism
  • Peroxisomes* / metabolism

Substances

  • Membrane Proteins
  • Adenosine Triphosphatases
  • ATPases Associated with Diverse Cellular Activities
  • PEX1 protein, human
  • PEX6 protein, human