Review article

Mitochondrial dysfunction induced by E-cigarettes

Where this started

Reading across the literature, the same signals kept appearing. One paper focused on oxidative stress, another on inflammation, another on metabolic disruption. Each was valid, but they rarely spoke to each other.

The question became unavoidable:
Are these really separate effects, or are they fragments of the same underlying process?

Why mitochondria?

Mitochondria are not just energy producers. They sit at the center of cellular decision-making, integrating stress signals, controlling metabolism, and regulating cell survival.

They are also unusually exposed. Their DNA sits close to the electron transport chain, constantly near reactive oxygen species, with limited repair capacity. That combination makes them both essential and fragile.

This made them a logical place to look for convergence.

What the evidence kept pointing to

Across different models and exposure systems, a pattern started to stabilize.

• Reactive oxygen species accumulate quickly after exposure
• Mitochondrial DNA shows signs of damage and instability
• Energy production drops as respiration becomes inefficient
• Membrane potential collapses, and calcium balance shifts
• Inflammatory signals amplify the damage rather than resolve it

What stood out was not any single mechanism, but how tightly they connect.
Once mitochondrial stress begins, it tends to sustain itself.

The part that complicates the narrative

Not all effects trace back neatly to nicotine. In many cases, flavoring chemicals and thermal degradation products appear to be more disruptive.

Aldehydes such as cinnamaldehyde interfere directly with mitochondrial metabolism. Metals from device components introduce additional oxidative burden. These exposures overlap and interact, making the system harder to interpret using single-factor explanations.

This complexity is often underestimated.

Why this perspective matters

Looking at mitochondria shifts the discussion.

Instead of asking:

• Does vaping affect the lungs?
• Does it affect the heart?
• Does it affect metabolism?

The question becomes:
What happens when cellular energy systems are persistently stressed?

From that angle, the downstream effects start to align more naturally across organ systems.

What still feels unresolved

Most of the current evidence comes from controlled systems: cells, animals, short-term exposures. These are useful, but they do not fully capture real-world patterns.

There are also methodological gaps:

• Mitochondrial dysfunction is often inferred rather than directly measured
• Exposure conditions vary widely across studies
• Long-term adaptation versus damage is still unclear

It is possible that early mitochondrial stress triggers adaptive responses. It is also possible that repeated exposure prevents recovery. Right now, both scenarios remain open.

Where this leads

This work does not close the question. It reframes it.

If mitochondrial dysfunction is a central node, then:

• Different toxicants may converge on the same biological outcome
• Seemingly unrelated diseases may share a common upstream trigger
• Interventions could target mitochondrial resilience rather than isolated pathways

That shift, from isolated effects to system-level disruption, is where the field may need to move next.

Reference

Sailis AB, Noh MABM, Leo BF, Faruqu FN, Yee A, Sim MS. Mitochondrial dysfunction induced by e-cigarettes. Toxicology. 2026;519:154339. https://doi.org/10.1016/j.tox.2025.154339