The role and importance of mitochondria is best reflected through their representation.
They are found in almost all types of human cells and in all multicellular life forms on Earth.
Mitochondria are tiny cell organelles, power plants or energy reservoirs that play a multiple role
in numerous biological processes and mechanisms. They have their own DNA (mtDNA) which
generally accounts for only 1% of the total cellular nucleic acid content and contain their own
small chromosomes. Mitochondria are inherited only from the mother.

Mitochondria are typically round to oval in shape and range in size from 0.5 to 3 μm. The
chemical energy produced by mitochondria is stored in a small molecule called adenosine
triphosphate (ATP). Most ATP is produced in mitochondria through a series of reactions, known
as oxidative phosphorylation (OXPHOS), and the citric acid cycle (Krebs cycle). In addition to
producing energy, mitochondria store calcium for cell signaling activities, generate heat, and
mediate cell growth and death.

Mitochondria play a vital role in allowing the skin to effectively maintain microbial
defense function and epidermal homeostasis. Primary mitochondrial disorders cause skin
manifestations that can be categorized into hair abnormalities, rashes, pigmentation
abnormalities, and acrocyanosis. Less attention has been paid to the fact that several skin
disorders are associated with the changes energy metabolism of mitochondria. Wide range of
skin disorders of primary or secondary mitochondrial pathology occurs and that a variety of
molecular defects can cause dysfunctional mitochondria.
Evidence suggests that mitochondria are vital regulators of skin physiology. The skin’s
epidermal progenitor cells are constantly dividing and making new cells to help the skin repair

itself and stay healthy. Their intense activity requires a lot of energy, which they get precisely
from ATP molecules. Mitochondria also play a role in melanocyte function and pigmentation.
Mitochondrial metabolism regulates keratinocyte differentiation by producing mitochondrial
reactive oxygen species (ROS), which are necessary to propagate the two types of signals that
promote epidermal differentiation. But also ROS can inflict oxidative damage on biomolecules
(e.g. proteins, lipids), resulting in loss of catalytic and/or structural integrity. Ultraviolet (UV)
radiation is known to cause oxidative stress in the skin causing damage to both nuclear and
mtDNA.

Mitochondrial role in skin aging
The skin is highly susceptible to photo-aging due to chronic exposure to solar UVA and
UVB radiations. Several studies have directly or indirectly linked mitochondrial dysfunction to
both chronological and photo-aging of the skin. Chronic UV exposure induces nuclear and
mitochondrial DNA damage and oxidative stress in the skin cells, which can progress to photo-
aging and or skin cancer. At the molecular levels, aged skin is characterized by damaged
mitochondria, mtDNA deletions, high ROS levels, and oxidative stress in both the dermal and
epidermal layers. Mutations and deletions in mtDNA are known to accumulate in post-
replicative tissues with aging, which is accompanied by a steady decline in mitochondrial
function, increased ROS production, and loss of mitochondrial membrane potential (MMP),
followed by increased mitophagy, and apoptosis.

Mitochondrial role in skin cancer
Although mitochondrial involvement in skin cancer has been investigated, further
research is still required as a clear understanding has not been established. Skin cancer risk is
linked to UV radiation, and the incidence of all skin cancer types have significantly increased in
the last 2–3 decades due to increased exposure to UV rays, both due to the thinning ozone layer
and frequent use of tanning beds. The risk of developing skin cancer, especially malignant
melanoma, is also higher in the Caucasian population on account of their lower cutaneous
melanin content. Mitochondria have been implicated in almost all human cancers, primarily on
account of their role in ROS generation and apoptosis.

Mitochondrial role in autoimmune skin diseases
Some autoimmune skin diseases, such as pemphigus vulgaris and lupus, are associated
with the presence of specific antibodies that belong to mitochondria. In people with lupus, these

changes in mitochondria affect the functioning of immune cells, reducing their energy and
increasing harmful molecules (ROS). In pemphigus vulgaris, the antibodies damage the
mitochondria in the skin cells, which causes a disruption in the breakdown of the cells and
further increases the harmful molecules.

Mitochondria disfunction and psoriasis
Psoriasis, a chronic inflammatory skin disorder affecting approximately 2–3% of the
global population, manifests as well-demarcated erythematous plaques, scaling, and pruritus. In
psoriasis, dysregulated immune responses and aberrant keratinocyte proliferation drive the
formation of characteristic plaques, accompanied by increased oxidative stress and mitochondrial
dysfunction within lesional skin. Mounting evidence indicates that mitochondrial reactive
oxygen species (mtROS) are involved in cellular signaling pathways, immune cell activation,
and epidermal hyperplasia, among other aspects of psoriasis.

Mitochondria disfunction and vitiligo
Another common dermatologic condition, vitiligo, has also been shown to have
mitochondrial influence. Vitiligo is a skin condition in which there is a loss of function of
melanocytes causing white skin lesions. Vitiligo pathogenesis is now found to be associated with
mitochondria. The complete absence of melanocytes at the lesioned site in vitiligo is a fact;
however, the precise mechanism of this destruction is still undefined. Evidence has demonstrated
that melanocyte function can be regulated by different types of skin cells via a melanogenic
cytokine network. Oxidative stress is considered a cause and trigger in the pathogenesis of
vitiligo, triggering further immune responses and causing melanocyte death. There is an
excessive accumulation of ROS (reactive oxygen species) due to damaged mitochondria, which
leads to an imbalance in melanocyte cells and ultimately to their damage. Changes of
mitochondria morphology and function to varying degrees have been shown in melanocytes,
keratinocytes, fibroblasts as well as other skin cells, and have been documented in lesional,
perilesional and nonlesional skin in patients with vitiligo.

Mitochondrial healthy
Targeted nutrition, lifestyle modifications, and nutritional supplements can help keep your
mitochondria healthy. A balanced diet rich in nutrients and antioxidants can help protect
mitochondria from oxidative stress and improve mitochondrial function. Supplements containing
these compounds can also be of great benefit to your cells. Some of the ingredients that are often
used in supplements and increasingly in beauty products to support mitochondrial health are:
alpha-ketoglutarate, fisetin, glycine, glucosamine, magnesium, coenzyme Q10, resveratrol, B
vitamins, omega-3 fatty acids, curcumin, L-carnitine, vitamins C.

Creating a proper skincare routine supports the preservation of proper mitochondrial
function. To support the health of your skin at the cellular level, you need to establish a routine
that will contribute to increasing the power of your skin cells. Use gentle cleansers to remove
impurities from the skin, then include antioxidant-rich serums to fight oxidative stress and
protect against damage, hydrating creams to strengthen the skin’s barrier, providing hydration,
and of course daily application of sunscreen to protect against UV rays.
References

1. Birch‐Machin, M. A. Mitochondria and skin disease. Clin. Exp. Dermatol. 25,
   141–146 (2000).
2. Alberts, B. et al. The Mitochondrion. in Molecular Biology of the Cell. 4th edition
   (Garland Science, 2002).
3. Armstrong, B. All about mitochondria: Definition and disease. Genomics
   Education Programme http://www.genomicseducation.hee.nhs.uk/blog/all-
   about-mitochondria-definition-and-disease/ (2023).
4. Duchen, M. R. Roles of Mitochondria in Health and Disease. Diabetes 53,
   S96–S102 (2004).
5. Feichtinger, R. G., Sperl, W., Bauer, J. W. & Kofler, B. Mitochondrial dysfunction: a
   neglected component of skin diseases. Exp. Dermatol. 23, 607–614 (2014).
6. Haas, R. H. Mitochondrial Dysfunction in Aging and Diseases of Aging. Biology 8,
   48 (2019).
7. Hussain, M. et al. Skin Abnormalities in Disorders with DNA Repair Defects,
   Premature Aging, and Mitochondrial Dysfunction. J. Invest. Dermatol. 141,
   968–975 (2021).
8. Karadağ, A. S. & Tursen, Ü. Supplements in Dermatology. (World Health
   Academy Publishing House, 2023).
9. Lin, Y. et al. The underestimated role of mitochondria in vitiligo: From oxidative
   stress to inflammation and cell death. Exp. Dermatol. 33, e14856 (2024).
10. Martic, I., Papaccio, F., Bellei, B. & Cavinato, M. Mitochondrial dynamics and
    metabolism across skin cells: implications for skin homeostasis and aging. Front.
    Physiol. 14, 1284410 (2023).
11. Naidoo, K., Hanna, R. & Birch-Machin, M. A. What is the role of mitochondrial
    dysfunction in skin photoaging? Exp. Dermatol. 27, 124–128 (2018).
12. Natarelli, N., Gahoonia, N., Aflatooni, S., Bhatia, S. & Sivamani, R. K. Dermatologic
    Manifestations of Mitochondrial Dysfunction: A Review of the Literature. Int. J.
    Mol. Sci. 25, 3303 (2024).
13. NOVOS. The Role of Mitochondria in Skin Health and Aging. NOVOS
    https://novoslabs.com/mitochondrias-influence-on-skin-health/ (2023).
14. Pizzorno, J. Mitochondria—Fundamental to Life and Health. Integr. Med. Clin. J.
    13, 8–15 (2014).
15. Sreedhar, A., Aguilera-Aguirre, L. & Singh, K. K. Mitochondria in skin health, aging,
    and disease. Cell Death Dis. 11, 1–14 (2020).
16. Mitochondria. https://www.genome.gov/genetics-glossary/Mitochondria.
17. Mitochondria: Form, function, and disease.
    https://www.medicalnewstoday.com/articles/320875 (2018).
18. 7 Ways To Support Your Mitochondria For Better Health & Ageing. Nutrition
    Diets https://nutritiondiets.co.uk/health/7-ways-to-support-your-mitochondria-
    for-better-health-and-ageing/ (2024).
19. Mitochondrion | Definition, Function, Structure, & Facts | Britannica.
    https://www.britannica.com/science/mitochondrion (2024).