Mitochondrial dysfunction: A hidden trigger of autism?

Abstract

Autism is a heterogeneous neurodevelopmental and neuropsychiatric disorder with no precise etiology. Deficits in cognitive functions uncover at early stages and are known to have an environmental and genetic basis. Since autism is multifaceted and also linked with other comorbidities associated with various organs, there is a possibility that there may be a fundamental cellular process responsible for this. These reasons place mitochondria at the point of interest as it is involved in multiple cellular processes predominantly involving metabolism. Mitochondria encoded genes were taken into consideration lately because it is inherited maternally, has its own genome and also functions the time of embryo development. Various researches have linked mitochondrial mishaps like oxidative stress, ROS production and mt-DNA copy number variations to autism. Despite dramatic advances in autism research worldwide, the studies focusing on mitochondrial dysfunction in autism is rather minimal, especially in India. India, owing to its rich diversity, may be able to contribute significantly to autism research. It is vital to urge more studies in this domain as it may help to completely understand the basics of the condition apart from a genetic standpoint. This review focuses on the worldwide and Indian scenario of autism research; mitochondrial abnormalities in autism and possible therapeutic approaches to combat it.

Keywords: Autism; Copy number variation (CNV); Mitochondria encoded genes; Neurodevelopmental disorder; World-wide scenario.

Figure 1

List of publications worldwide focusing on mitochondrial dysfunction in autism. • 1–5 = Mexico (02), Brazil (04), Africa (03), Europe (05), North Korea (06), Israel (02), Argentina (02), Russia (01), Denmark (02), Venzuela (02) and Norway (05) • 6–10 = India (10), South Korea (06), Saudi Arabia (10), Australia (10), China (09), Ohio (06), Germany (08) and France (06) • 11–15 = Japan (14) and UK (15) • 16–20 = Canada (18) • <20 = USA (110).

Figure 2

Graph depicting the number of studies over a period of 30 years in India and word-wide.

Figure 3

mTOR role in autophagy of Autism. Impaired autophagy due to increased mTOR, giving rise to reduced spine pruning resulting in elevated spine numbers as compared with normally functioning autophagy within the cell.

Figure 4

NRF-2 in autism treatment. Activators and inhibitors of NRF-2 are used to ameliorate the symptoms of autism by providing protection from oxidative stress. When NRF-2 is activated, it translocates to the nucleus, activating ARE genes which release anti-inflammatory, antibiotic and antioxidant enzymes that may help in alleviating the oxidative stress.

Figure 5

Treatment of defective mitochondria. This figure represents the possible therapeutic techniques that can be used for the treatment of defective mitochondria. When defects in ETC is observed, correct tRNAs can be imported through gene technology into the mitochondria. These tRNAs will replicate using the cellular machinery providing correct proteins; PPAR ligands can be introduced to increase the replication of mitochondrial genes to enhance the availability of suitable genes; antigenomic drugs can also be administered to inhibit replication of defective genes in the mitochondria.