By Niti Singh

Many of us take our mitochondria—the powerhouse of the cell—for granted. However, there are numerous mitochondrial diseases that can severely impair its functioning and our well-being; the most common of these diseases is MELAS, which stands for mitochondrial encephalopathy with lactic acidosis and stroke-like episodes. 

Breaking the name down, mitochondrial encephalopathy refers to the damage done to the functioning of the mitochondria in cellular respiration (a process used to generate ATP, or energy, for the cell), specifically oxidative phosphorylation (MELAS Syndrome, 2025a). Oxidative phosphorylation generates large amounts of energy through the creation of a proton gradient that requires several proteins to function; the genetic disorder referred to by mitochondrial encephalopathy causes the proteins needed for oxidative phosphorylation to function abnormally, causing ATP production to decrease. 

As a response to this lack of cellular respiration, lactic acid fermentation occurs to generate smaller amounts of energy. As the name suggests, this type of fermentation creates lactic acid that is stored in the human body. Lactic acidosis is the result of the buildup of lactic acid in the bloodstream; this can cause nausea, fatigue, and several other issues in the human body (Henry et al., n.d.). Stroke-like episodes occur because of a lack of energy production in the brain; these are stroke-like because they are non-ischemic and are rather caused by mitochondrial dysfunction. 

The inheritance pattern of traditional MELAS is quite simple. Since mitochondrial DNA is mostly inherited from the mother, the presence of the disorder in the mother determines if a child will have the disorder. This genetic disorder is caused by mtDNA mutations, with the most common one being the m.3243A>G mutation in the MT-TL1 gene (Pia & Lui, 2024). This gene codes for the creation of a specific transfer RNA, or tRNA, crucial for protein synthesis in the mitochondria. Due to this mutation, the synthesis of specific proteins is impaired, causing issues with oxidative phosphorylation, chemiosmosis, and overall energy production. 

In extremely rare cases, however, nuclear DNA mutations can also cause this disorder, as certain proteins for the mitochondria do originate from the nucleus (Henry et al., n.d.). One such mutation can be inherited from either the mother or father, as both contribute to the nuclear DNA of an individual.

Several tests are conducted before a patient is diagnosed with MELAS. For instance, if a patient experiences stroke-like episodes, has seizures frequently, and has evidence of mitochondrial myopathy (muscle weakness proven through ragged-red fibers), tests are performed that observe the presence of more specific symptoms of MELAS in a patient. The age of onset varies, but most people who are diagnosed with the disorder are minors aged 2 to 10 years old (Pia & Lui, 2024).  

There are various symptoms of MELAS that range in intensity. For instance, headaches, frequent muscle aches, and vision problems are signature symptoms of MELAS that are largely caused by the lactic acidosis and mitochondrial encephalopathy. These symptoms also vary in intensity due to a concept called heteroplasmy. As each cell has its own mtDNA for each mitochondrion, if only a few mitochondria in most cells have the mutation with the disorder while others function normally, the individual may not exhibit any symptoms of the disorder or simply have mild versions of them. However, if an individual has a majority of their cells with the disorder, they may experience incredibly strong symptoms of the disorder, and their quality of life may be significantly impacted due to the disease. 

While there is no known treatment that can completely cure MELAS, most medications target the symptoms of MELAS (MELAS Syndrome, 2025). For instance, many of the symptoms of MELAS are caused by a lack of nitric oxide in the body—which is thought to be caused by endothelial functions. Therefore, many of the medications for MELAS aim to increase the amount of nitric oxide in the body. Doctors often administer arginine and citrulline, both of which increase the amount of nitric oxide produced (MELAS Syndrome, 2025). Other treatment options aim to enhance oxidative phosphorylation to increase ATP production, such as coenzyme Q10, menadione, and vitamin K1. 

Sources:

Pia, S., & Lui, F. (2024, January 25). Melas Syndrome. StatPearls – NCBI Bookshelf.
https://www.ncbi.nlm.nih.gov/books/NBK532959/

MELAS Syndrome. (2025, June 2). Cleveland Clinic.
https://my.clevelandclinic.org/health/diseases/25149-melas-syndrome

Henry, C., Patel, N., Shaffer, W., Murphy, L., Park, J., & Spieler, B. (n.d.). Mitochondrial
encephalomyopathy with lactic acidosis and Stroke-Like Episodes—MELAS syndrome.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5625994/

MELAS Syndrome. (2025a, March 18). rarediseases.org. Retrieved July 29, 2025, from
https://rarediseases.org/rare-diseases/melas-syndrome/