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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...
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...
Structure of Porins01:21

Structure of Porins

Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a  motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel 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...
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...

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Related Experiment Video

Updated: Jun 19, 2026

Methodology for Accurate Detection of Mitochondrial DNA Methylation
12:11

Methodology for Accurate Detection of Mitochondrial DNA Methylation

Published on: May 20, 2018

Reverse engineering of BNIP3 identifies a mitochondrial protective peptide.

Ulrike B Hendgen-Cotta1, Anna Roth2, Christine Beuck3

  • 1Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. ulrike.hendgen-cotta@uk-essen.de.

Nature Communications
|June 17, 2026
PubMed
Summary
This summary is machine-generated.

Researchers identified key activators of mitochondrial cell death, leading to the development of a novel peptide therapeutic (B-017) that protects tissues from damage by targeting mitochondrial dysfunction.

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An Integrated Approach for Microprotein Identification and Sequence Analysis
09:37

An Integrated Approach for Microprotein Identification and Sequence Analysis

Published on: July 12, 2022

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Last Updated: Jun 19, 2026

Methodology for Accurate Detection of Mitochondrial DNA Methylation
12:11

Methodology for Accurate Detection of Mitochondrial DNA Methylation

Published on: May 20, 2018

An Integrated Approach for Microprotein Identification and Sequence Analysis
09:37

An Integrated Approach for Microprotein Identification and Sequence Analysis

Published on: July 12, 2022

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Mitochondria are crucial in disease, but drug development faces challenges due to poor understanding of cell death regulators.
  • The BH3-only protein BNIP3 is implicated in mitochondrial cell death pathways.

Purpose of the Study:

  • To elucidate the upstream molecular regulators of mitochondrial fate.
  • To identify and characterize the functional domain of BNIP3 responsible for activating cell death.
  • To develop a therapeutic agent targeting BNIP3-mediated mitochondrial cell death.

Main Methods:

  • Structural modeling and sequence-function analysis of BNIP3's N-terminus.
  • Development of a BNIP3 antagonist peptide (B-017).
  • In vitro assays using human cells and in vivo studies in animal models (heart, brain, liver).

Main Results:

  • Identified a critical functional domain and amino acid hotspots in BNIP3's N-terminus that activate BCL-2 executioner proteins.
  • Developed B-017, a peptide that specifically inhibits BNIP3-BCL-2 interactions, preserving mitochondrial integrity.
  • B-017 showed target specificity, a good safety profile, suppressed cell death signaling, and reduced tissue damage in animal models.

Conclusions:

  • BNIP3 is a key activator of mitochondrial cell death through BCL-2 protein interaction.
  • B-017 is a potent and specific therapeutic candidate for diseases involving mitochondrial dysfunction.
  • Targeting BNIP3 offers a promising strategy to mitigate tissue damage in various clinical conditions.