Mitochondrial and peroxisomal fission in cortical neurogenesis

The human brain is unique in its cellular diversity, intricate cytoarchitecture, function, and complex metabolic and bioenergetic demands, for which mitochondria and peroxisomes are essential. Mitochondria are multifunctional organelles that coordinate various signaling pathways central to neurogenesis. The dynamic morphological changes of the mitochondrial network have been linked to the regulation of bioenergetic and metabolic states. Specific protein machinery is dedicated to mitochondrial fission and fusion, allowing organelle distribution during cell division, organelle repair, and adaptation to environmental stimuli (excellent reviews have been published on these topics [Kondadi and Reichert, 2024; Giacomello et al., 2020; Tilokani et al., 2018; Kraus et al., 2021; Navaratnarajah et al., 2021]). In parallel, peroxisomes contain over 50 different enzymes which regulate metabolic functions that are critical for neurogenesis (Berger et al., 2016; Hulshagen et al., 2008). Peroxisomes share many of the components of their fission machinery with the mitochondria and undergo fission to help meet metabolic demands in response to environmental stimuli (Schrader et al., 2016). This review focuses primarily on the machinery involved in mitochondrial and peroxisomal fission. Mitochondrial fission has been identified as a critical determinant of cell fate decisions (Iwata et al., 2023, 2020; Khacho et al., 2016; King et al., 2021; Prigione and Adjaye, 2010; Vantaggiato et al., 2019; Kraus et al., 2021). The connection between alterations in peroxisomal fission and metabolic changes associated with cellular differentiation remains less clear. Here, we provide an overview of the functional and regulatory aspects of the mitochondrial and peroxisomal fission machinery and provide insight into the current mechanistic understanding by which mitochondrial and peroxisomal fission influence neurogenesis.