Sep 2026· Current Opinion in Neurobiology· Vol 101, pp. 103270 - 103270· 0 citations· 78 references
Medicine
TL;DR
These findings challenge the conventional view of mitochondria as generic metabolic engines and position mitochondrial molecular diversity as a fundamental feature of brain organization, with direct relevance to behavior, aging, and neurological disease.
Abstract
Mitochondria are not uniform organelles. Across the brain, they exhibit profound molecular, biochemical, and functional diversity shaped by cell type, anatomical region, subcellular compartment, and lived experience. Recent advances in cell-type- and subcellular domain-targeted proteomics, transcriptomics, advanced live imaging, and functional biochemistry have begun to map this landscape with unprecedented resolution. Together, these findings challenge the conventional view of mitochondria as generic metabolic engines and position mitochondrial molecular diversity as a fundamental feature of brain organization, with direct relevance to behavior, aging, and neurological disease. This mini review synthesizes key recent studies in this field, highlighting their findings, methodological novelty, and significance, and formulates theories and hypotheses for future investigations.
Mitochondria are traditionally viewed as a homogeneous network supporting cellular energy production. However, increasing evidence reveals substantial heterogeneity across biological scales, from intramitochondrial microdomains to specialised mitochondrial populations within cells and tissues. These subpopulations diff...
P. Desmaison, Giulia Bertolin· Communications Biology· 0 citations
ABSTRACT Mitochondria-associated ER membranes (MAMs) are inter-organelle contact sites that mediate signaling between the ER and mitochondria. MAMs play crucial roles in Ca2+ transfer, lipid metabolism, mitochondrial respiration, protein homeostasis, autophagy, and ER stress. In the central nervous system (CNS), these...
Eun Jin Jang, Jisoo Lee, Seung-Ha Shin et al.· Animal Cells and Systems· 0 citations
Our textbook view of mitochondria, which has been shaped by studies in animals and yeast, fails to do justice to the organelle's broader eukaryotic diversity. While most mitochondria retain a tiny genome, the overwhelming majority of their proteins are nuclear-encoded and vary extensively across lineages. To map this d...
The brain is a highly complex organ composed of diverse, specialized cell types whose coordinated functions underpin cognition and behavior. While extensive research has elucidated neuronal signaling mechanisms, the metabolic interactions between distinct brain cells that sustain energy homeostasis are not yet comprehe...
Carmen Lahr, Elle Wilson, Melanie Sengupta et al.· Neurobiology of Disease· 0 citations
The metabolism of neuronal activity is highly localized and cannot be sustained by cell-wide distribution of energy. Neurons and glia organize metabolic enzymes, mitochondria, lipid droplets, and endoplasmic reticulum (ER) contacts into spatially localized microdomains that dynamically couple energy generation to synap...
S. Mohammad, A. K. Kareem, M. Rekha et al.· Neurochemistry International· 0 citations
Lipids are fundamental components of the brain, crucial for synaptic transmission and signal propagation. Altered brain lipid composition is associated with common and rare neuropathologies, yet, the spatial organization of the mammalian brain lipidome remains insufficiently characterized compared to other modalities1–...
Luca Fusar Bassini, H. H. Schede, Laura Capolupo et al.· bioRxiv· 7 citations
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