Mitochondrial Dysfunction, Macrophage, and Microglia in Brain Cancer

Abstract

Glioblastoma (GBM) is the most common malignant brain cancer. Increasing evidence suggests that mitochondrial dysfunction plays a key role in GBM progression as mitochondria is essential in regulating cell metabolism, oxidative stress, and cell death. Meanwhile, the immune microenvironment in GBM is predominated by tumor-associated macrophages and microglia (TAM), which is a heterogenous population of myeloid cells that, in general, create an immunosuppressive milieu to support tumor growth. However, subsets of TAMs can be pro-inflammatory and thereby antitumor. Therapeutic strategies targeting TAMs are increasingly explored as novel treatment strategies for GBM. The connection between mitochondrial dysfunction and TAMs phenotype in the tumor microenvironment is unclear. This review aims to provide perspectives and discuss possible molecular mechanisms mediating the interplay between glioma mitochondrial dysfunction and TAMs phenotype in shaping tumor immune microenvironment.

Mitochondria and Brain Disease: A Comprehensive Review of Pathological Mechanisms and Therapeutic Opportunities

“…As mentioned, mitochondria play a crucial role in controlling cellular metabolism, oxidative stress, and apoptosis. Tumour-associated macrophages and microglia (TAM) are a heterogeneous population of myeloid cells that, in general, provide an immunosuppressive milieu to support tumour growth and dominate the immune microenvironment in GBM [ 253 ].…”

Engineering Exosomes to Specifically Target the Mitochondria of Brain Cells

“…These powerhouses of the cell are responsible for producing energy and regulating cellular metabolism, making them crucial components of overall cellular health. Dysfunctional mitochondria have been linked to various diseases, including myocardial infarction, hypertension, AD, PD, and brain tumors . There are several reasons why targeting mitochondria may be beneficial in treating these conditions. , For instance, enhancing ATP production can help restore energy balance within cells, which is often disrupted in neurodegenerative diseases .…”

Long noncoding RNA HOXC-AS3 remodels lipid metabolism and promotes the proliferation of transformed macrophages in the glioma stem cell microenvironment by regulating the hnRNPA1/CaM axis

“…TAM significantly contribute to the construction of a highly immunosuppressive GME dominated by GSC [ 10 ]. Recently, the molecular mechanism by which macrophage transform into TAM within the protumor GBM immune microenvironment (GIME) stimulated by GSC has been widely investigated [ 11 , 12 ].…”