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

18.4K
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...
18.4K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

12.3K
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,...
12.3K
Autophagic Cell Death01:18

Autophagic Cell Death

4.3K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.3K
Mitochondria01:37

Mitochondria

19.6K
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,...
19.6K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

8.3K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

4.6K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.6K

You might also read

Related Articles

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

Sort by
Same author

The Sirt2-Nur77 axis regulates muscle stem cell quiescence and senescence via epigenetic-metabolic synergy.

Cell death & disease·2026
Same author

The p53 R181C mutation accumulates through impaired deacetylation by Sirt1 and facilitates tumor development.

Communications biology·2026
Same author

Enhanced insulin signaling via circulating ATG7: A potential therapeutic strategy for diabetes.

Proceedings of the National Academy of Sciences of the United States of America·2025
Same author

Beyond the nucleus: the ATM-CHEK2 axis senses mtROS to orchestrate mitophagy.

Autophagy·2025
Same author

DNA damage response pathway regulates Nrf2 in response to oxidative stress.

Science advances·2025
Same author

The deubiquitination-PARylation positive feedback loop of the USP10-PARP1 axis promotes DNA damage repair and affects therapeutic efficacy of PARP1 inhibitor.

Oncogene·2025

Related Experiment Video

Updated: Jan 16, 2026

Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome
07:56

Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome

Published on: November 30, 2022

5.9K

Mitochondrial ROS triggers mitophagy through activating the DNA damage response signaling pathway.

Qi-Qiang Guo1,2, Shan-Shan Wang1,2, Xiao-You Jiang1,2

  • 1The College of Basic Medical Science, Health Sciences Institute, China Medical University, Shenyang 110122, Liaoning, China.

Proceedings of the National Academy of Sciences of the United States of America
|September 30, 2025
PubMed
Summary

Mitochondrial ROS activate the ATM-CHK2 DNA damage pathway, initiating mitophagy to clear damaged mitochondria. This pathway is crucial for cellular protection against oxidative stress and tissue damage.

Keywords:
ATMCHK2PINK1mitophagymtROS

More Related Videos

Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima
09:13

Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima

Published on: August 12, 2018

15.6K
Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy
09:29

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy

Published on: May 4, 2016

7.5K

Related Experiment Videos

Last Updated: Jan 16, 2026

Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome
07:56

Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome

Published on: November 30, 2022

5.9K
Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima
09:13

Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima

Published on: August 12, 2018

15.6K
Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy
09:29

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy

Published on: May 4, 2016

7.5K

Area of Science:

  • Cellular Biology
  • Mitochondrial Dynamics
  • DNA Damage Response

Background:

  • Mitochondrial reactive oxygen species (mtROS) and mitophagy are key in cellular stress responses.
  • The precise mechanisms translating oxidative stress into mitophagy remain incompletely understood.

Purpose of the Study:

  • To elucidate the signaling pathway linking mtROS production to adaptive mitophagy.
  • To identify key molecular players involved in this stress-induced response.

Main Methods:

  • Investigated the role of the ATM-CHK2 DNA damage response pathway in mtROS signaling.
  • Utilized biochemical assays to determine CHK2 phosphorylation targets in mitophagy.
  • Examined mitophagy induction in Chk2 knockout mice under oxidative stress conditions.

Main Results:

  • mtROS activate the ATM-CHK2 pathway, which acts as a central regulator of mitophagy.
  • CHK2 phosphorylates ATAD3A, OPTN, and Beclin 1, orchestrating PINK1 accumulation, mitochondrial targeting, and autophagosome formation.
  • Chk2-/- mice exhibit impaired mitophagy and recovery in a renal ischemia-reperfusion model.

Conclusions:

  • A novel mtROS-triggered signaling cascade involving ATM-CHK2 coordinates mitophagy.
  • This pathway is essential for cellular and tissue protection against pathophysiological damage.