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Updated: Oct 19, 2025
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Understanding the Changes in Mitochondrial Morphology through Dynamic and Three-dimensional Fluorescence Micrographs
Published on: August 15, 2025
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The fasting-feeding metabolic transition regulates mitochondrial dynamics
Mauricio Castro-Sepúlveda1,2, Béatrice Morio3, Mauro Tuñón-Suárez1
1Laboratorio de Ciencias del Ejercicio, Escuela de Kinesiologia, Facultad de Medicina, Universidad Finis Terrae, Santiago, Chile.
Summary
Human metabolic flexibility (MetFlex) involves how the body switches between fasting and feeding. This study shows that this transition alters mitochondria-ER interactions, leading to mitochondrial fission and reduced cristae density in human cells.
Area of Science:
- Cellular biology
- Metabolic research
- Mitochondrial dynamics
Background:
- Insulin resistance in humans is linked to impaired metabolic flexibility (MetFlex), the ability to transition between fasting and feeding states.
- Mitochondrial dynamics are suggested as a key factor in MetFlex, but this has not been investigated in humans.
- Peripheral blood mononuclear cells (PBMCs) offer a model to study human metabolic responses.
Purpose of the Study:
- To investigate mitochondrial dynamics during the fasting-to-feeding transition in human PBMCs.
- To explore the role of endoplasmic reticulum (ER)-mitochondria calcium (Ca2+) exchange in regulating mitochondrial dynamics.
- To assess the relevance of PBMCs in obesity and low MetFlex contexts using mouse models.
Main Methods:
- Human PBMCs were isolated from subjects after a 16-hour fast and after consuming a glucose load.
- Mitochondrial dynamics were analyzed using electron microscopy.
- In vitro experiments involved treating PBMCs with an IP3R inhibitor (Xestospongin B) to study ER-mitochondria Ca2+ signaling.
- Mouse lymphocytes from wild-type and obese (ob/ob) mice were used for comparative analysis.
Main Results:
- The fasting-to-feeding transition in human PBMCs decreased mitochondria-ER interactions, induced mitochondrial fission, and reduced mitochondrial cristae density.
- In vitro studies indicated that IP3R activity is crucial for the mitochondrial dynamic response to substrate availability.
- Mitochondria-ER interactions were confirmed to be regulated by the fasted-fed transition in mouse lymphocytes, with evidence of miscommunication in diabetic mouse PBMCs.
Conclusions:
- The fasting/feeding transition impacts mitochondrial structure and ER-mitochondria communication in human PBMCs.
- IP3R activity appears to play a significant role in mediating these mitochondrial dynamic changes.
- PBMCs serve as a valuable model for studying metabolic flexibility and its disruption in conditions like diabetes and obesity.
Keywords:
fastingmitochondria-ER interactionmitochondrial cristaemitochondrial fusionmitochondrial morphologyobesityMore Related Videos
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