When Mitochondria Call for Help

What New Science Reveals About Energy Shortage, Stress, and the ERM Framework

A new scientific review published in Mitochondrion takes us deep inside the cell—right to the entry gates of the mitochondria, the tiny “power stations” that keep us alive. What the authors discovered maps beautifully onto a concept we use often at Healing Passion: Exposure-Related Malnutrition (ERM).

The message is powerful:

When your cells don’t have enough energy, they start losing the ability to repair, recover, and maintain themselves—and they activate emergency programs to survive.

Let’s break this down in simple terms.

Mitochondria Need Energy to Make Energy

Most people know mitochondria produce ATP—the energy currency we use for everything from thinking to detoxifying to repairing injuries.

But here’s a lesser-known truth:

Mitochondria also need ATP in order to function, repair themselves, and import the proteins required to keep the engine running.

Inside every cell, more than 1,000 proteins must be delivered into mitochondria. These proteins go through special “import gates” called TOMM and TIMM.

Like airports, these gates require electricity and trained staff. If the lights go out (low ATP), nothing moves.

When energy drops:

• The gates slow down

• Proteins pile up outside

• Stress signals rise

• Damage accumulates

This is the beginning of what the new review calls mitochondrial import stress.

And this is exactly where ERM starts.

Low Energy → Cellular Stress Alerts

When protein import slows, the mitochondria fire off SOS signals.

The review highlights three emergency systems:

1️⃣ ISR – Integrated Stress Response

Think of this as the citywide emergency broadcast.

The cell temporarily slows down protein production to conserve resources and shifts its priorities to survival, not growth.

2️⃣ UPRmt – Mitochondrial Stress Response

This is the internal repair team.

The cell increases production of chaperones—special proteins that refold or remove damaged components.

3️⃣ UPRam – Cytosolic Cleanup System

If misdelivered proteins spill into the cytosol (the cell’s “streets”), cleanup crews activate to prevent toxic buildup.

All of these responses attempt to help mitochondria recover.

But there is a limit.

If Recovery Fails → Mitophagy (Selective Removal of Mitochondria)

If a mitochondrion is too damaged or too starved of ATP to be repaired, the cell makes a difficult choice:

It removes the failing mitochondrion to protect the whole system.

This process is called mitophagy, and it’s actually healthy—in moderation.

But when energy shortage is chronic, ongoing mitophagy eventually reduces the total mitochondrial population.

Fewer mitochondria → lower metabolic capacity → fatigue, weakness, brain fog, and vulnerability to chronic disease.

This pattern matches one of the most important insights of ERM:

Chronic energy mismatch leads to structural loss, not just functional symptoms.

Where ERM Fits In: The Big Picture

ERM describes a state where the body is pushed into chronic adaptation due to:

• stress

• inflammation

• toxins

• nutrient shortages

• sleep disruption

• chronic infection

• etc.

These exposures force mitochondria to run in “survival mode” rather than “repair mode.”

What this new review shows is that:

✔️ Even small energy drops disrupt mitochondrial maintenance

Low ATP = impaired import machinery.

✔️ The body tries to compensate

ISR + UPRmt = adaptive effort to recover.

✔️ But if stress continues, the system shifts from adaptation to loss

Mitophagy removes too many mitochondria → metabolic reserve collapses.

This is why people in ERM often describe:

• “I crash easily.”

• “I don’t recover like I used to.”

• “Small stressors overwhelm me.”

• “My energy feels fragile.”

These are not “mysterious” symptoms—they are the predictable consequences of bioenergetic insufficiency.

Why This Matters for Health, Aging, and Chronic Disease

This new research helps explain:

Why some people feel exhausted even with normal lab results

Energy stress occurs before organ damage is visible.

Why recovery requires more than rest

Mitochondria must repair their import machinery to rebuild capacity.

Why aging accelerates under chronic stress

Less energy → more mitophagy → fewer mitochondria → metabolic slowdown.

Why brain fog and mood issues are common in ERM

The brain depends heavily on mitochondrial import for neurotransmitter balance and repair.

Takeaway

This paper provides elegant mechanistic support for the ERM framework:

When energy is insufficient, cells shift into survival mode.They try to repair.If they can’t, they start dismantling themselves to stay alive.

Restoring energy availability—through nutrition, sleep, stress recovery, detoxification, and metabolic support—is not optional.

It is the foundation of resilience.

Calais, H., & Bertolin, G. (2025). Stress at the gates: Mitochondrial import dysfunctions, response pathways, and therapeutic potential. Mitochondrion, 102, 102107. https://doi.org/10.1016/j.mito.2025.102107