The DNA binding parvulin Par17 is targeted to the mitochondrial matrix by a recently evolved prepeptide uniquely

Daniel Kessler1, Panagiotis Papatheodorou, Tina Stratmann

  • 1Department of Structural and Medicinal Biochemistry, Center for Medical Biotechnology - ZMB, University of Duisburg-Essen, 45117 Essen, Germany. daniel.kessler@uni-due.de

BMC Biology
|September 19, 2007
PubMed
Abstract

Insights

The newly discovered parvulin Par17, found in humans but not other mammals, targets the mitochondrial matrix. This DNA-binding protein represents a novel component of the human mitochondrial proteome.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Evolutionary Biology

Background:

  • Parvulin-type peptidyl prolyl cis/trans isomerase Par14 is highly conserved across metazoans.
  • The recently identified parvulin Par17 possesses a unique N-terminal domain, prompting investigation into its evolutionary occurrence and functional role.

Purpose of the Study:

  • To investigate the evolutionary presence and subcellular localization of parvulin Par17.
  • To determine the functional characteristics of Par17, including its mitochondrial targeting and DNA-binding capabilities.

Main Methods:

  • Genomic analysis of Par17 exon sequences across 10 primate species.
  • Subcellular fractionation and immunofluorescence microscopy of human cell lysates.
  • Mitochondrial import assays and DNA-binding assays under varying salt conditions.

Main Results:

  • Par17 is encoded in Hominidae genomes (including humans) but absent in other mammalian species studied.
  • Endogenous Par17 localizes to mitochondria and membrane fractions, with EGFP fusions co-localizing with mitochondrial markers.
  • Par17 exhibits salt-resistant association with mitochondria, is imported into the mitochondrial matrix dependent on membrane potential, and binds double-stranded DNA.

Conclusions:

  • Parvulin Par17 is a DNA-binding protein specifically targeted to the mitochondrial matrix.
  • Its mitochondrial targeting is mediated by a recently evolved mitochondrial prepeptide.
  • Par17 represents a novel protein constituent of the Hominidae mitochondrial proteome.

Related Concept Videos

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,...
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial precursors...
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Animal Mitochondrial Genetics02:59

Animal Mitochondrial Genetics

Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...