Episode Details

In this Energy Code Deep Dive, Dr. Mike Belkowski and co-host Don Bailey unpack a striking 2025 paper by Liu and colleagues on gastrointestinal cancers (especially gastric and colorectal tumors) and why we may be looking in the wrong place for answers.

Instead of focusing only on DNA mutations, this episode explores the mitochondria as the cell’s decision-makers; the organelles that help determine whether a cell grows, rests, or dies. The hosts break down the paper’s framework of mitochondrial quality control (MQC) into three core pillars: biogenesis (make), dynamics (shape), and mitophagy(break/recycle).

They explain how tumors hijack these systems to fuel growth, metastasis, and drug resistance — and how therapies may work by disrupting the cancer cell’s energy code, not just damaging DNA. The conversation also covers PGC-1α, fission/fusion proteins, mitophagy under hypoxia, chemo resistance, and a fascinating (and very weird) malaria-related finding that reinforces the core concept.

The big takeaway: cancer may be less about a broken blueprint and more about a corrupted energy system.

(Educational content only, not medical advice.)

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Article Discussed in Episode:

The role of mitochondrial biogenesis, mitochondrial dynamics and mitophagy in gastrointestinal tumors

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Key Quotes From Dr. Mike:

“There is no one-size-fits-all energy code.”

“Cancer isn’t just a genetic accident, it’s a fundamental corruption of how the cell handles energy.”

“The shape of the mitochondria literally determines how well chemotherapy works.”

“Cancer operates in a Goldilocks zone.”

“Proton beam therapy… also works by hacking the energy code.”

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Key points

1. GI cancers remain a massive global burden
   • The episode opens with sobering numbers: millions of new GI tumor cases and deaths annually.
   • Focus is specifically on gastric and colorectal cancers.
2. The paper shifts focus from DNA to mitochondria
   • Modern oncology often centers on mutations.
   • This review argues mitochondria are not just “batteries” — they are decision-makers controlling cell fate.
3. Cancer is framed as a corruption of the “energy code”
   • The hosts describe tumors as hijacking mitochondrial decision-making.
   • Cancer rewrites the systems that regulate growth, dormancy, and apoptosis.
4. Mitochondrial Quality Control (MQC) is the core framework
   • The paper’s model has three pillars:
     • Biogenesis (making mitochondria)
     • Dynamics (shaping mitochondria via fission/fusion)
     • Mitophagy (recycling damaged mitochondria)
   • The hosts summarize this as: “make, shape, and break.”
5. Pillar 1: Biogenesis fuels tumor growth
   • Tumors need energy to expand, so they ramp up mitochondrial production.
   • PGC-1α is presented as the key “foreman” regulating this process.
6. Cancer operates in a biogenesis Goldilocks zone
   • Some biogenesis is necessary for tumor growth.
   • But too much PGC-1α can push cells into apoptosis (cell death), making it a fragile balance.
7. Excess biogenesis can become toxic to cancer
   • Overproduction of mitochondria can trigger death pathways (via BAX/Bak-type mitochondrial apoptosis signaling, as described in the transcript).
   • This creates a therapeutic opportunity: push tumor energy systems beyond their tolerance.
8. Tumors actively silence genes that would normalize metabolism