Related Experiment Video

Updated: Jun 9, 2026

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
15:04

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils

Published on: September 28, 2019

Inhibition of human peptide deformylase disrupts mitochondrial function

Sindy Escobar-Alvarez1, Jeffrey Gardner, Aneesh Sheth

  • 1Molecular Pharmacology and Chemistry, Sloan-Kettering Institute, New York, NY 10065, USA.

Molecular and Cellular Biology
|September 1, 2010
PubMed

Insights

Human peptide deformylase (HsPDF) in mitochondria is crucial for making proteins essential for cellular energy production. Inhibiting HsPDF impairs respiratory function and ATP levels, impacting cell survival.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Peptide deformylases (PDFs) are metalloproteases that remove N-formyl-methionine from peptides.
  • The human homolog, HsPDF, is located in mitochondria, but its cellular function is unknown.
  • Mitochondria contain formylated substrates, suggesting a role for HsPDF.

Purpose of the Study:

  • To elucidate the cellular function of human peptide deformylase (HsPDF) within mitochondria.
  • To investigate the role of HsPDF in mitochondrial translation and oxidative phosphorylation.

Main Methods:

  • Utilized structurally different HsPDF inhibitors and control peptidase inhibitors.
  • Assessed the impact of HsPDF inhibition on mitochondrial DNA-encoded protein accumulation.
  • Measured respiratory function and cellular ATP levels.

Main Results:

  • HsPDF is necessary for the accumulation of mitochondrial DNA-encoded proteins.
  • Inhibition of HsPDF disrupts the assembly of new respiratory complexes.
  • HsPDF inhibition reduces respiratory function and ATP production, leading to reliance on glycolysis.

Conclusions:

  • HsPDF plays a vital role in maintaining mitochondrial respiratory function.
  • HsPDF is essential for mitochondrial translation and oxidative phosphorylation complex biogenesis.
  • The function of HsPDF in mitochondria is analogous to that of chloroplast PDF.

More Related Videos

Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment07:55

Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment

Published on: September 25, 2017

Using Live Cell STED Imaging to Visualize Mitochondrial Inner Membrane Ultrastructure in Neuronal Cell Models08:48

Using Live Cell STED Imaging to Visualize Mitochondrial Inner Membrane Ultrastructure in Neuronal Cell Models

Published on: June 30, 2023

Related Concept Videos

ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
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...
The Electron Transport Chain01:30

The Electron Transport Chain

The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...
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...
Mitochondria01:37

Mitochondria

Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...