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Developmental Regulation of Mitochondrial Apoptosis by c-Myc Governs Age- and Tissue-Specific Sensitivity to Cancer

Kristopher A Sarosiek1, Cameron Fraser2, Nathiya Muthalagu3

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Mayer 430, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.

Cancer Cell
|December 27, 2016
PubMed

Insights

Adult tissues resist apoptosis due to refractory mitochondria, unlike young tissues. This difference, linked to c-Myc expression, may explain chemotherapy toxicities in pediatric cancer patients.

Area of Science:

  • Cellular biology
  • Mitochondrial function
  • Apoptosis

Background:

  • Healthy tissues display variable sensitivity to toxic stimuli.
  • Understanding this variability is crucial for predicting treatment outcomes.

Purpose of the Study:

  • To investigate the reasons behind differential tissue sensitivity to apoptosis.
  • To explore the role of mitochondria in cellular resistance to chemotherapy and radiation.

Main Methods:

  • Utilized BH3 profiling to assess mitochondrial sensitivity to apoptosis.
  • Compared mitochondrial function in adult and young mice and human tissues.
  • Investigated the role of c-Myc in regulating apoptotic protein expression.

Main Results:

  • Adult somatic tissues (brain, heart, kidneys) exhibit mitochondria refractory to pro-apoptotic signals.
  • Mitochondria in young tissues are primed for apoptosis, increasing susceptibility to genotoxic damage.
  • c-Myc drives apoptotic protein expression in young tissues, linking growth and cell death.

Conclusions:

  • Mitochondrial refractoriness to apoptosis in adult tissues confers resistance to cytotoxic therapies.
  • Developmental differences in apoptotic priming may explain treatment-associated toxicities in pediatric cancer patients.
Keywords:
apoptosisc-Myccardiotoxicitycell death regulationchemosensitivityneurotoxicitypediatric cancerradiosensitivityside effects of chemotherapyside effects of radiation therapy

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