Mitophagy: Maintaining the integrity of the Cell by Elimination of Dysfunctional Mitochondria

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A human cell may contain from 2 to 2,500 mitochondria, depending on tissue type, antioxidant status, and other factors.   The functional mitochondria in the cell are the active mitochondria and the more functional mitochondria, the stronger is the health of the cell.

A biological theory states that mitochondrial number and function determine human longevity.   It is proposed that age-related declines in mitochondrial content and function not only affect physical function, but also play a major role in regulation of life span. Regular aerobic exercise and prevention of adiposity by healthy diet may increase healthy life expectancy and prolong life span through beneficial effects at the level of the mitochondrion.  1  2

The dysfunction of the mitochondria occurs more rapidly than any other components of the cell.  Mitochondrial degradation and dysfunction occurs as a result of the aging process.   A healthy population of mitochondria is critical for the well-being of cells.

These dysfunctional mitochondria have to be removed from the cell. Because of the danger of having damaged mitochondria in the cell, the timely elimination of damaged and aged mitochondria is essential for maintaining the integrity of the cell. This turnover process consists of the sequestration and hydrolytic degradation by the lysosome, a process also known as mitophagy.  3

mitophagy

Mitophagy is the selective degradation of mitochondria by autophagy. It often occurs to defective mitochondria following damage or stress.  The occurrence of mitophagy is not limited to the damaged mitochondria but also involves undamaged ones.  4

The dysfunctional mitochondria release hazardous materials, particularly when they have been compromised by damage or age. Accordingly, ensuring proper elimination of dysfunctional mitochondria is imperative to cellular survival, and mitochondrial damage has been implicated in aging, 5 diabetes, and neurodegenerative diseases.  6

Mutations in mitochondrial DNA, due to the aging process, can cause mitophagy to become less efficient.  Eventually, damaged mitochondria build up, leading to cell death.  7 

There are certain identified substances that enhance autophagy and thus probably apply to mitophagy:

  • Nicotinamide treatment decreases mitochondrial content and helps cells maintain high mitochondrial quality.  8
  • Wogonin and luteolin, have been shown cancer cell death through inhibition of autophagy.  9  10  11
  • Ginsenosides such as F2 have also been shown to exhibit anti-cancer effects through the modulation of autophagy.  12
  • Naphthazarin, a naphthoquinone compound, is a microtubule depolymerising agent that induces cell death by activating apoptosis and autophagy.  13
  • Plumbagin induces G2-M arrest and autophagic cell death by inhibiting the AKT/mTOR (mammalian target of rapamycin) pathway in breast cancer cells.  14
  • Berberine exhibits its anti-cancer effects by inducing autophagic cell death and mitochondrial apoptosis in liver cancers.  15
  • Tetrandrine acts as an enhancer of autophagy that induces early G1 arrest in colon carcinoma cells.  16

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