Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

13.3K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
13.3K
The Electron Transport Chain01:30

The Electron Transport Chain

16.7K
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...
16.7K
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

6.3K
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
6.3K
Structure of Porins01:21

Structure of Porins

3.0K
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...
3.0K
ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

14.6K
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...
14.6K
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

3.0K
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...
3.0K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Functional implications of the conformational landscape of a multidrug transporter revealed by Zebrafish Abcb4 structures.

Nature communications·2026
Same author

Recent advances in structural investigations of cancer antigen mesothelin and its interactions with therapeutic antibodies.

Antibody therapeutics·2026
Same author

Functional Implications of the Conformational Landscape of a Multidrug Transporter Revealed by Structures of Zebrafish Abcb4.

bioRxiv : the preprint server for biology·2025
Same author

Conformations of Bcs1L undergoing ATP hydrolysis suggest a concerted translocation mechanism for folded iron-sulfur protein substrate.

Nature communications·2024
Same author

Point mutations in Arf1 reveal cooperative effects of the N-terminal extension and myristate for GTPase-activating protein catalytic activity.

PloS one·2024
Same author

A concerted ATPase cycle of the protein transporter AAA-ATPase Bcs1.

Nature communications·2023

Related Experiment Video

Updated: Jul 2, 2025

Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays
08:03

Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays

Published on: March 7, 2025

557

Mitochondrial Cytochrome bc1 Complex as Validated Drug Target: A Structural Perspective.

Lothar Esser1, Di Xia1

  • 1Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 37 Convent Drive, Room 2122C, Bethesda, MD 20892, USA.

Tropical Medicine and Infectious Disease
|February 23, 2024
PubMed
Summary

Structural insights into cytochrome bc1 complex function and inhibition are crucial for developing new antibiotics, pesticides, and anti-parasitic drugs. Understanding structural differences helps overcome drug resistance and reduce cytotoxicity.

Keywords:
complex IIIcytochrome bc1 complexcytotoxicityinhibitor bindingselectivity

More Related Videos

Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1
13:15

Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1

Published on: February 25, 2016

11.9K
Exploring Mitochondrial Energy Metabolism of Single 3D Microtissue Spheroids Using Extracellular Flux Analysis
08:15

Exploring Mitochondrial Energy Metabolism of Single 3D Microtissue Spheroids Using Extracellular Flux Analysis

Published on: February 3, 2022

3.1K

Related Experiment Videos

Last Updated: Jul 2, 2025

Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays
08:03

Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays

Published on: March 7, 2025

557
Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1
13:15

Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1

Published on: February 25, 2016

11.9K
Exploring Mitochondrial Energy Metabolism of Single 3D Microtissue Spheroids Using Extracellular Flux Analysis
08:15

Exploring Mitochondrial Energy Metabolism of Single 3D Microtissue Spheroids Using Extracellular Flux Analysis

Published on: February 3, 2022

3.1K

Area of Science:

  • Biochemistry
  • Structural Biology
  • Drug Discovery

Background:

  • Mitochondrial respiratory chain Complex III (cytochrome bc1 complex) is a key target for various therapeutic and agricultural agents.
  • Existing knowledge on cytochrome bc1 complex function and inhibition is substantial, yet challenges persist regarding drug resistance and cytotoxicity.

Purpose of the Study:

  • To review the structural aspects of cytochrome bc1 complexes and their inhibitors.
  • To elucidate mechanisms of drug resistance and cytotoxicity from a structural perspective.
  • To explore strategies for developing novel drugs by exploiting structural differences.

Main Methods:

  • Analysis of atomic-resolution structures of various cytochrome bc1 complexes.
  • Examination of structures with bound inhibitors to understand conformational changes and Q-cycle mechanism implications.
  • Correlation of structural details with sequence changes to explain drug resistance.

Main Results:

  • Detailed structural features of different cytochrome bc1 complexes are presented.
  • Conformational changes and Q-cycle mechanism insights derived from inhibitor-bound structures.
  • Structural basis for drug resistance identified through coupled sequence and structural analysis.

Conclusions:

  • Structural perspective is vital for addressing challenges in cytochrome bc1 complex-targeted drug development.
  • Exploiting evolutionary conserved enzyme structural differences can enhance antifungal drug selectivity and reduce cytotoxicity.
  • Atomic-level structural insights provide a unique approach to overcoming drug resistance and improving therapeutic outcomes.