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Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

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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,...
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Export of Mitochondrial and Chloroplast Genes02:19

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A eukaryotic cell can have up to three different types of genetic systems: nuclear, mitochondrial, and chloroplast. During evolution, organelles have exported many genes to the nucleus; this transfer is still ongoing in some plant species. Approximately 18% of the Arabidopsis thaliana nuclear genome is thought to be derived from the chloroplast’s cyanobacterial ancestor, and around 75% of the yeast genome derived from the mitochondria’s bacterial ancestor. This export has occurred...
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Mitochondria01:37

Mitochondria

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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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Animal Mitochondrial Genetics02:59

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Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
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Comparing Mitochondrial, Chloroplast, and Prokaryotic Genomes02:16

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The present-day mitochondrial and chloroplast genomes have retained some of the characteristics of their ancestral prokaryotes and also have acquired new attributes during their evolution within eukaryotic cells. Like prokaryotic genomes, mitochondrial and chloroplast genomes neither bind with histone-like proteins nor show complex packaging into chromosome-like structures, as observed in eukaryotes. Unlike mitotic cell divisions observed in eukaryotic cells, mitochondria and chloroplasts...
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Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

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Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
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Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue
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mtKO: A dedicated guide RNA library for mitochondria research.

Karambir Kaur1, Javeria Zaheer1, Fengchao Lang1

  • 1Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892.

Proceedings of the National Academy of Sciences of the United States of America
|July 17, 2025
PubMed
Summary

Mitochondria are vital in cancer. A new CRISPR screen reveals the antioxidant enzyme SOD2 is crucial for IDH1-mutated cancers, highlighting a potential therapeutic target in Krebs cycle-deficient tumors.

Keywords:
CRISPR screenIDH1SOD2metabolismmitochondria

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Area of Science:

  • Mitochondrial biology and cancer metabolism.
  • Functional genomics and CRISPR screening.

Background:

  • Mitochondria play crucial roles in both normal physiology and disease, particularly in cancer.
  • Cancer cells reprogram mitochondrial metabolism to meet increased energy demands, especially those with pre-existing metabolic alterations.
  • Understanding mitochondria-associated pathways is key to targeting cancer development.

Purpose of the Study:

  • To develop and utilize a CRISPR screening platform (mtKO) for unbiased identification of critical mitochondria-associated pathways in cancer.
  • To pinpoint key mitochondrial factors supporting cancer progression.
  • To investigate the role of mitochondrial pathways in IDH1-mutated cancers.

Main Methods:

  • Development of a robust CRISPR screening platform named mitochondria Knockout (mtKO).
  • Application of the mtKO screen to identify essential mitochondria-associated genes and pathways.
  • Mechanistic studies to elucidate the role of identified factors in cancer pathogenesis.

Main Results:

  • The mtKO screen identified the mitochondrial antioxidant enzyme SOD2 as essential for cells with IDH1 mutations.
  • SOD2 activity was found to be critical for the manifestation of IDH1-mutated cancers.
  • SOD2 maintains redox homeostasis and mitochondrial fitness, impacting disease progression.

Conclusions:

  • The study introduces a powerful functional genomic tool (mtKO) for identifying mitochondrial-centered pathways.
  • SOD2 is a critical vulnerability in IDH1-mutated, Krebs cycle-deficient cancers.
  • These findings offer potential therapeutic strategies targeting mitochondrial vulnerabilities in specific cancer types.