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Related Concept Videos

Mitochondrial Membranes01:45

Mitochondrial Membranes

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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,...
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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.
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During the electron transport chain, electrons from NADH and FADH2 are first transferred to complexes I and II, respectively. These two complexes then transfer the electrons to ubiquinol, which carries them further to complex III. Complex III passes the electrons across the intermembrane space to Cyt c, which carries them further to complex IV. Complex IV donates electrons to oxygen and reduces it to water. As electrons pass through complexes I, III, and IV, the energy released aids the pumping...
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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,...
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Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
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Updated: Jun 11, 2025

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Physioxia rewires mitochondrial complex composition to protect stem cell viability.

Janice Raabe1, Ilka Wittig2, Patrick Laurette3

  • 1Institute of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.

Redox Biology
|September 28, 2024
PubMed
Summary
This summary is machine-generated.

Physioxic culture (5% O2) of human induced pluripotent stem cells (hiPSCs) enhances chromosomal stability and pluripotency. This method reduces oxidative phosphorylation and senescence, optimizing hiPSC function for research.

Keywords:
ComplexesHIF1αHuman induced pluripotent stem cellsMitochondrial functionNDUFA4L2Senescence

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Area of Science:

  • Stem Cell Biology
  • Cellular Respiration
  • Genomics and Proteomics

Background:

  • Human induced pluripotent stem cells (hiPSCs) are crucial for studying human biology.
  • Oxygen levels during hiPSC culture significantly impact cell viability and function.
  • Understanding optimal oxygen conditions is vital for maintaining hiPSC quality.

Purpose of the Study:

  • To investigate the mechanistic impact of physioxic (5% O2) versus hyperoxic (20% O2) culture on hiPSCs.
  • To assess effects on chromosomal stability, pluripotency, and cellular metabolism.
  • To elucidate molecular changes in mitochondrial function and protein composition.

Main Methods:

  • Reprogramming dermal fibroblasts into hiPSCs from 52 individuals.
  • Culture under physioxic (5% O2) and hyperoxic (20% O2) conditions.
  • Proteomic profiling, Giemsa-banding for karyotyping, Stage-Specific Embryonic Antigen 3 (SSEA-3) staining, glucose/lactate assays, RNA-seq, ATAC-seq, and mitochondrial assays.

Main Results:

  • Physioxic hiPSCs showed significantly less chromosomal mosaicism (6% vs. 32%) and higher SSEA-3 positivity.
  • Physioxic culture led to reduced oxidative phosphorylation, lower senescence markers (IGFBP3, β-galactosidase), and altered mitochondrial complex composition (e.g., NDUFA4L2, ATP5IF1).
  • RNA- and ATAC-seq revealed a hypoxic transcription factor-binding footprint, including increased NDUFA4L2 expression and chromatin accessibility.

Conclusions:

  • Physioxic culture improves hiPSC chromosomal stability and pluripotency compared to hyperoxic conditions.
  • This optimized culture environment downregulates oxidative phosphorylation and senescence pathways.
  • Physioxic culture induces significant re-wiring of mitochondrial complex composition, enhancing hiPSC suitability for research.