Related Experiment Video

Updated: Apr 7, 2026

Resin-Assisted Capture Coupled with Isobaric Tandem Mass Tag Labeling for Multiplexed Quantification of Protein Thiol Oxidation
07:16

Resin-Assisted Capture Coupled with Isobaric Tandem Mass Tag Labeling for Multiplexed Quantification of Protein Thiol Oxidation

Published on: June 21, 2021

2.3K

Alkbh8 Regulates Selenocysteine-Protein Expression to Protect against Reactive Oxygen Species Damage

Lauren Endres1, Ulrike Begley2, Ryan Clark2

  • 1Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, Albany, New York 12203, United States of America; RNA Institute and Cancer Research Center, University at Albany, State University of New York, Albany, New York 12222, United States of America.

Plos One
|July 7, 2015
PubMed

Insights

The tRNA methyltransferase Alkbh8 regulates cellular responses to oxidative stress by controlling the expression of key antioxidant enzymes. Its absence leads to increased reactive oxygen species (ROS) damage, highlighting Alkbh8

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Reactive oxygen species (ROS) from environmental and metabolic sources cause cellular damage, contributing to diseases like cancer and neurodegeneration.
  • Gene expression regulation, including translational control, is crucial for preventing ROS-induced damage.
  • Cellular oxidative stress responses are vital for disease prevention, and their deficiencies are linked to aging and various pathologies.

Purpose of the Study:

  • To investigate the role of tRNA methyltransferase Alkbh8 in the translational regulation of oxidative-stress response enzymes.
  • To elucidate the mechanism by which Alkbh8 controls the expression of ROS detoxification enzymes.
  • To define the contribution of Alkbh8 and tRNA modifications to cellular defense against oxidative stress.

Main Methods:

  • Utilized a gene-targeted knockout mouse embryonic fibroblast (MEF) system (Alkbh8-/- MEFs).
  • Analyzed ROS levels, DNA and lipid damage markers, and cellular stress hallmarks.
  • Investigated the induction of Alkbh8 in response to ROS and its role in selenocysteine-containing enzyme expression (glutathione peroxidases and thioredoxin reductase).
  • Examined the impact of oxidative stress on tRNA modification (mcm5Um) and its correlation with ROS detoxification enzyme expression.

Main Results:

  • Alkbh8-/- MEFs exhibited elevated ROS levels, increased DNA and lipid damage, and cellular stress.
  • Alkbh8 expression is induced by ROS and is essential for the efficient translation of selenocysteine-containing ROS detoxification enzymes.
  • Oxidative stress induces the tRNA modification mcm5Um, enhancing ROS detoxification enzyme expression in normal MEFs.
  • This damage-induced tRNA reprogramming and stop-codon recoding were impaired in Alkbh8-/- MEFs.

Conclusions:

  • Alkbh8 and specific tRNA modifications (mcm5Um) are central regulators of cellular oxidative stress responses in mammals.
  • Alkbh8 plays a critical role in preventing DNA and lipid damage by controlling the expression of antioxidant enzymes.
  • The study introduces a new animal model for environmental and cancer research, linking translational control to damage prevention.

More Related Videos

Author Spotlight: Advancing Structural and Biochemical Studies of Proteins Through Thermal Shift Assays03:09

Author Spotlight: Advancing Structural and Biochemical Studies of Proteins Through Thermal Shift Assays

Published on: August 9, 2024

1.6K
Defining Hsp33's Redox-regulated Chaperone Activity and Mapping Conformational Changes on Hsp33 Using Hydrogen-deuterium Exchange Mass Spectrometry10:24

Defining Hsp33's Redox-regulated Chaperone Activity and Mapping Conformational Changes on Hsp33 Using Hydrogen-deuterium Exchange Mass Spectrometry

Published on: June 7, 2018

9.3K

Related Concept Videos

Sulfur Assimilation01:20

Sulfur Assimilation

Sulfur is an essential element in biological systems, contributing to synthesizing key biomolecules, including amino acids such as cysteine and methionine, and cofactors such as coenzyme A and biotin. Microorganisms primarily assimilate sulfur as sulfate (SO₄²⁻) from the environment, which must undergo a series of biochemical transformations before it can be incorporated into cellular components. As sulfate is highly oxidized, it must undergo assimilatory sulfate reduction to...
507
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
9.9K
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
2.0K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

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...
19.6K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
39.0K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.5K