Bioenergetics: Open Access

Role of Oxidative Phosphorylation and Glycolysis in Monocyte Immune Response

Castilho Lopez^* Department of Animal Biology, University of Campinas, Campinas, Brazil
^*Correspondence: Castilho Lopez, Department of Animal Biology, University of Campinas, Campinas, Brazil, Email:

Received: 27-May-2024, Manuscript No. BEG-24-27429; Editor assigned: 29-May-2024, Pre QC No. BEG-24-27429 (PQ); Reviewed: 12-Jun-2024, QC No. BEG-24-27429; Revised: 19-Jun-2024, Manuscript No. BEG-24-27429 (R); Published: 26-Jun-2024, DOI: 10.35248/2167-7662.24.12.265

Description

Monocytes, a type of white blood cell, play a central role in the body’s immune defense mechanisms, acting as key regulators of immune responses and adaptively responding to pathogens and inflammation. Monocyte bioenergetics the energy processes that power these cells is a fundamental aspect of immunometabolism, an emerging field exploring how metabolic pathways interact with immune function. As researchers delve deeper into monocyte bioenergetics, it becomes increasingly clear that these energy pathways are tightly linked to immune response modulation, impacting everything from infection responses to inflammatory diseases. This article provides an in-depth look at the bioenergetic pathways within monocytes, how these pathways support immune function and the broader implications for human health.

Monocytes are constantly in circulation, prepared to act in response to infection or injury. They are equipped with various bioenergetic pathways that support their adaptability. These include glycolysis, Oxidative Phosphorylation (OXPHOS) and fatty acid oxidation. Each of these pathways allows monocytes to respond quickly and effectively to changing demands. Glycolysis is a rapid, anaerobic (oxygen-independent) process that produces ATP, the cell’s energy currency, which is often prioritized when an immediate response is needed. In contrast, oxidative phosphorylation is an oxygen-dependent pathway occurring within the mitochondria that generates a more sustained ATP supply, vital for long-term responses and cell function. Fatty acid oxidation also contributes to monocyte energy, providing additional resources during prolonged immune responses.

The balance between glycolysis and oxidative phosphorylation determines how monocytes react to various immune challenges. During inflammation or infection, monocytes tend to increase their reliance on glycolysis, an energy-efficient pathway that produces ATP rapidly. This shift enables them to activate more quickly, a response that is critical during the early stages of infection or tissue damage.

Glycolysis plays a particularly significant role in monocyte activation and function. When monocytes detect an infection or inflammatory signal, they undergo a metabolic shift that enhances glycolytic activity. This transition is not merely an increase in energy production; it is also an essential aspect of monocyte activation. During glycolysis, certain intermediate products, such as lactate, accumulate within monocytes and signal them to increase their immune activities. This leads to the production of cytokines, molecules that help amplify immune responses and promotes monocyte transformation into more active forms, including macrophages and dendritic cells.

Research has shown that this glycolytic shift is regulated by specific signaling pathways, such as the hypoxia-inducible factor-1α (HIF-1α) pathway. Under conditions of low oxygen or high metabolic demand, HIF-1α helps activate genes involved in glycolysis, ensuring monocytes have a ready ATP supply for immediate immune responses. This glycolytic dependency is especially significant in diseases with chronic inflammation, as monocytes remain in a prolonged state of activation, driving sustained inflammatory responses.

Oxidative Phosphorylation (OXPHOS) takes place in mitochondria, the organelles that generate energy through the electron transport chain. For monocytes, OXPHOS is a slower yet more efficient pathway than glycolysis. When monocytes are not actively responding to infection, they rely more on OXPHOS to maintain a stable energy supply, supporting cellular maintenance and repair functions. Mitochondrial health is thus essential for monocyte function; damage or dysfunction in mitochondria can impair OXPHOS, affecting monocyte ability to respond to immune signals properly.

Studies have shown that monocytes in a resting state have a higher reliance on mitochondrial oxidative phosphorylation, which conserves resources and provides a steady ATP output over extended periods. Mitochondrial respiration allows monocytes to prepare for future responses without depleting energy reserves. Additionally, mitochondrial health influences monocyte lifespan and overall immune response capability. Dysfunctions in mitochondrial OXPHOS have been observed in aging and in chronic inflammatory diseases, leading to a reduced immune capacity and an increased vulnerability to infections.

Fatty Acid Oxidation (FAO) is another key pathway in monocyte bioenergetics, especially during prolonged immune activation. In FAO, fatty acids are broken down in the mitochondria to produce ATP, offering an alternative energy source when glycolysis and OXPHOS alone may not meet cellular demands. FAO is particularly relevant in the context of chronic inflammation, where monocytes must sustain their activation over long periods. FAO provides monocytes with a continuous energy source, supporting their metabolic flexibility and enabling them to maintain immune activity even under high demand.

Studies have found that monocytes exhibit higher FAO rates in certain disease states, such as obesity and diabetes, where chronic inflammation places significant stress on the immune system. While FAO provides energy sustainability, an overreliance on FAO in monocytes has been linked to increased inflammation, suggesting that a balanced FAO pathway is necessary to prevent hyperactive immune responses that could lead to tissue damage.

Monocytes can undergo metabolic reprogramming, shifting between glycolysis, OXPHOS and FAO depending on immune requirements. This reprogramming enables monocytes to meet the diverse demands of immune function. During infection, monocytes prioritize glycolysis for rapid activation, producing energy quickly while promoting cytokine production. After the initial immune response, monocytes may shift back to oxidative phosphorylation and fatty acid oxidation to sustain long-term immune functions and maintain cellular energy balance.