Related Experiment Video

Updated: Jun 26, 2026

Isolating Potentiated Hsp104 Variants Using Yeast Proteinopathy Models
08:44

Isolating Potentiated Hsp104 Variants Using Yeast Proteinopathy Models

Published on: November 11, 2014

A molecular chaperone for mitochondrial complex I assembly is mutated in a progressive encephalopathy

Isla Ogilvie1, Nancy G Kennaway, Eric A Shoubridge

  • 1Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.

The Journal of Clinical Investigation
|October 4, 2005
PubMed

Insights

NADH:ubiquinone oxidoreductase (complex I) deficiency, a cause of mitochondrial disease, is linked to assembly defects. Researchers identified B17.2L as a crucial molecular chaperone essential for complex I assembly and nervous system function.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Genetics

Background:

  • NADH:ubiquinone oxidoreductase (complex I) deficiency is a frequent cause of mitochondrial oxidative phosphorylation disorders.
  • Clinical manifestations in infants include Leigh syndrome, cardiomyopathy, and encephalomyopathy.
  • Assembly defects of the complex I holoenzyme are implicated in at least 50% of patient cases, with unknown molecular chaperones.

Observation:

  • Whole genome subtraction of yeast identified B17.2L, a paralogue of the B17.2 structural subunit, as a candidate assembly factor.
  • A null mutation in B17.2L was identified in a patient with progressive encephalopathy.
  • Retroviral expression of B17.2L rescued the complex I assembly defect in patient fibroblasts.

Findings:

  • B17.2L acts as a molecular chaperone essential for mammalian complex I assembly.
  • An anti-B17.2L antibody recognized an 830-kDa subassembly in patients with complex I assembly defects.
  • B17.2L coimmunoprecipitated with complex I structural subunits from human heart mitochondria.

Implications:

  • B17.2L is critical for the assembly and function of complex I.
  • Understanding B17.2L's role opens new avenues for diagnosing and potentially treating complex I assembly defects.
  • This discovery is vital for comprehending the molecular basis of mitochondrial diseases affecting the nervous system.

More Related Videos

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

Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes08:56

Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes

Published on: October 10, 2025

Related Concept Videos

Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
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...
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...
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...
Energy to Drive Translocation01:37

Energy to Drive Translocation

Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Molecular Chaperones and Protein Folding03:00

Molecular Chaperones and Protein Folding

The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...