Dynamic properties of mitochondria during human corticogenesis

Abstract

Mitochondria are signaling hubs responsible for the generation of energy through oxidative phosphorylation, the production of key metabolites that serve the bioenergetic and biosynthetic needs of the cell, calcium (Ca2+) buffering and the initiation/execution of apoptosis. The ability of mitochondria to coordinate this myriad of functions is achieved through the exquisite regulation of fundamental dynamic properties, including remodeling of the mitochondrial network via fission and fusion, motility and mitophagy. In this Review, we summarize the current understanding of the mechanisms by which these dynamic properties of the mitochondria support mitochondrial function, review their impact on human cortical development and highlight areas in need of further research.

Cell Biology Meets Cell Metabolism: Energy Production Is Similar in Stem Cells and in Cancer Stem Cells in Brain and Bone Marrow

“…[36][37][38] Regarding the mitochondrial network, mitochondrial fusion that produces highly elongated mitochondria supports efficient OXPHOS, whereas mitochondrial fission that results in smaller and rounded mitochondria promotes glycolysis and greater biosynthesis of anabolic precursors. 39,40 It appeared that in all glioblastoma cells investigated be it differentiated cells or GSCs, the morphology of mitochondria is deviant from normal cells. Mitochondria in glioblastoma cells are generally small, with very dense matrices and disorganized cristae, which is in line with the assumption that glycolysis is used by cancer cells for ATP production because of defective mitochondria.…”

Mitochondria in Neurogenesis: Implications for Mitochondrial Diseases

“…Conversely, in adult neurogenesis mitochondria in intermediate progenitor cells show increased fused morphology compared to undifferentiated neural stem cells 65 . Despite these minor differences, it is widely accepted that mitochondria undergo changes during neurogenesis to eventually acquire an elongated morphology in neurons 15,17 …”

“…Among somatic cells, neurons are known to be highly dependent on mitochondrial function, given the high energy demand of the brain, which consumes around 20% of energy at rest despite weighting only around 2% of the entire human body 13 . Recent evidence indicates that mitochondria could play a role not only in energetically demanding mature cells like neurons, but also in governing cell fate decisions during the establishment of physiological neurogenesis 14‐17 …”

The balance of mitochondrial fission and fusion in cortical axons depends on the kinases SadA and SadB

“…Of particular importance for neuronal homeostasis are mitochondria. Defects in their morphology or dynamics lead to neurodevelopmental diseases and neurodegeneration (Baum and Gama, 2021). Mitochondria are dynamic organelles that continuously remodel their morphology by fission and fusion (Fenton et al, 2021;Moore and Holzbaur, 2018).…”