Bioenergetics: Open Access

Role of Mitochondrial Impairment in Risperidone’s Bioenergetic Effects

Camila Chatre^* Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
^*Correspondence: Camila Chatre, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy, Email:

Received: 27-May-2024, Manuscript No. BEG-24-27430; Editor assigned: 29-May-2024, Pre QC No. BEG-24-27430 (PQ); Reviewed: 12-Jun-2024, QC No. BEG-24-27430; Revised: 19-Jun-2024, Manuscript No. BEG-24-27430 (R); Published: 26-Jun-2024, DOI: 10.35248/2167-7662.24.12.266

Description

Risperidone, an antipsychotic medication commonly used to treat conditions such as schizophrenia, bipolar disorder and irritability associated with autism, has been associated with bioenergetic disruptions at the cellular level. While the drug can alleviate symptoms of psychosis and mood disorders effectively, emerging research points to potential impacts on mitochondrial function and overall energy metabolism. This article examines the effects of risperidone on cellular bioenergetics, emphasizing the metabolic pathways affected and their implications for patients.

Risperidone functions primarily by acting on dopamine D2 and serotonin 5-HT2A receptors. This dual receptor antagonism helps reduce psychotic symptoms by modulating neurotransmitter activity, stabilizing mood and diminishing hallucinations and delusions. However, beyond its effect on the central nervous system, risperidone has been observed to impact cellular structures such as mitochondria, which serve as the energy powerhouses of the cell. These structures play an important role in energy production through processes like oxidative phosphorylation and any disruption in mitochondrial function can affect cell viability, leading to metabolic disturbances.

The primary bioenergetic disruption associated with risperidone use centers on mitochondrial dysfunction. Mitochondria generate Adenosine Triphosphate (ATP) through oxidative phosphorylation, a process that depends on the proper functioning of the Electron Transport Chain (ETC). Studies suggest that risperidone may impact the ETC’s efficiency, reducing ATP production and resulting in decreased cellular energy availability.

This reduction in ATP has wide-ranging consequences. Cells require consistent energy supplies to perform various functions, from synthesizing proteins and repairing DNA to maintaining ion gradients essential for cellular signaling. When ATP production declines, cells may switch from oxidative phosphorylation to anaerobic glycolysis, a less efficient means of energy production that leads to an accumulation of lactate, potentially affecting overall cellular health.

Risperidone has been linked to increased oxidative stress within cells. When mitochondrial function is impaired, the electron transport chain may produce higher levels of Reactive Oxygen Species (ROS), including superoxide and hydrogen peroxide. Under normal conditions, cells manage these molecules through antioxidant mechanisms, such as superoxide dismutase and glutathione peroxidase, which neutralize ROS and prevent cellular damage.

However, when ROS production exceeds the cell’s antioxidant capacity, oxidative stress occurs, leading to cellular damage. Proteins, lipids and DNA can suffer oxidative damage, which affects cellular function and may trigger cell death pathways. In neurons, excessive oxidative stress may disrupt signaling pathways and contribute to neurodegenerative processes. This aspect of risperidone-induced bioenergetic disruption has raised concerns about the drug’s potential long-term effects on brain health, particularly in populations using the medication chronically.

Mitochondrial impairment in risperidone-treated cells may lead to metabolic shifts, particularly in glucose utilization. Normally, cells rely on oxidative phosphorylation for efficient energy production; however, when this process is compromised, cells may turn to glycolysis, a pathway that converts glucose to pyruvate, producing ATP in the absence of oxygen.

This shift towards glycolysis can result in a phenomenon known as the Warburg effect, where cells depend on glycolysis even when oxygen is available. Though this pathway allows cells to continue generating ATP despite mitochondrial dysfunction, it is less efficient and leads to an increase in lactic acid production. Higher lactic acid levels can disrupt cellular pH and contribute to acidosis, which further impacts cellular function. In tissues sensitive to metabolic changes, such as the brain, a shift in glucose metabolism can impair neurotransmitter synthesis, potentially affecting cognitive function.

In response to mitochondrial dysfunction, cells may initiate compensatory adaptations, including mitochondrial biogenesis. This process involves the creation of new mitochondria to offset impaired energy production. However, risperidone may influence pathways associated with mitochondrial biogenesis, including peroxisome Proliferator-activated Receptor Gamma Coactivator-1 Alpha (PGC-1α) signaling. PGC-1α is a master regulator of mitochondrial biogenesis and is activated in response to energy demands.

If risperidone suppresses PGC-1α activity, cells may struggle to compensate for mitochondrial deficits, leading to persistent energy shortages. Over time, this bioenergetic imbalance could exacerbate the effects of oxidative stress and cellular aging, particularly in energy-demanding tissues such as muscle and brain tissue. Additionally, mitochondrial DNA damage, which can accumulate as a result of oxidative stress, may impair the generation of functional mitochondria, compounding bioenergetic challenges.

When energy deficits and oxidative stress reach critical levels, cells may activate apoptosis, a programmed cell death pathway. Mitochondria play an essential role in apoptosis through the release of cytochrome C which activates a cascade of proteolytic enzymes that dismantle cellular components. The balance between cellular survival and apoptosis depends on energy availability and the extent of oxidative stress. Persistent mitochondrial dysfunction may tip this balance toward cell death, leading to tissue damage over time.

In the brain, excessive apoptosis due to mitochondrial dysfunction and oxidative stress may contribute to neurodegenerative processes, potentially affecting cognitive function. While research is ongoing, some studies suggest a connection between long-term antipsychotic use and neurocognitive side effects, which may, in part, be due to bioenergetic disruptions.