Related Experiment Video

Updated: May 20, 2026

Transmitochondrial Cybrid Generation Using Cancer Cell Lines
07:49

Transmitochondrial Cybrid Generation Using Cancer Cell Lines

Published on: March 17, 2023

Impact of mitochondrial reductive stress due to respiratory chain limitation on cancer via posttranslational

Christos Chinopoulos1

  • 1Department of Biochemistry, Semmelweis University, Budapest, Hungary.

Redox Biology
|May 18, 2026
PubMed

Insights

Respiratory chain limitation in tumors alters cellular chemistry by impacting oxygen availability and redox balance. This influences various posttranslational modifications, affecting tumor growth and adaptation.

Area of Science:

  • Biochemistry
  • Cancer Biology
  • Metabolic Regulation

Background:

  • Respiratory chain limitation is a common, heterogeneous state in solid tumors.
  • Hypoxia, electron transport chain defects, and therapeutic interventions drive this limitation.
  • This state leads to reduced electron flow, altered metabolite pools, and reactive oxygen species generation.

Purpose of the Study:

  • To review how electron transport chain limitation impacts posttranslational modifications (PTMs) in tumors.
  • To elucidate the mechanisms by which respiratory chain defects remodel PTMs.
  • To understand the context-dependent nature of PTM alterations in cancer.

Main Methods:

  • Review of existing literature on respiratory chain function and PTMs in cancer.
  • Analysis of biochemical pathways affected by electron transport chain limitation, including oxygen partitioning and redox balance.
  • Integration of knowledge on how these metabolic shifts influence specific PTMs.

Main Results:

  • Electron transport chain limitation remodels PTMs via oxygen partitioning and redox backpressure.
  • Oxygen availability, controlled by respiratory complex IV, affects dioxygenase activity, influencing hydroxylation and demethylation.
  • Redox shifts impact NAD(P)+/NAD(P)H balance, metabolite pools, and thiol buffering, altering numerous PTMs.

Conclusions:

  • Respiratory chain limitation creates a PTM-routing state dependent on location and tumor environment.
  • Specific PTMs like lysine acylations, histone methylation, and ADP-ribosylation are significantly remodeled.
  • Understanding these PTM alterations is crucial for comprehending tumor adaptation and developing targeted therapies.
Keywords:
DioxygenasesHypoxiaNAD(+)/NADH ratioReverse electron transferSirtuinsUbiquinone

More Related Videos

Isolation of Mitochondria for Mitochondrial Supercomplex Analysis from Small Tissue and Cell Culture Samples05:45

Isolation of Mitochondria for Mitochondrial Supercomplex Analysis from Small Tissue and Cell Culture Samples

Published on: May 3, 2024

Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry08:19

Assessing Mitochondrial Function in Sciatic Nerve by High-Resolution Respirometry

Published on: May 5, 2022

Related Concept Videos

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...
Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
The Electron Transport Chain01:30

The Electron Transport Chain

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 in...
Mitochondria01:37

Mitochondria

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,...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

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...
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,...