Related Experiment Video
Updated: May 10, 2026
Understanding the Changes in Mitochondrial Morphology through Dynamic and Three-dimensional Fluorescence Micrographs
Published on: August 15, 2025
Bioenergetic flux, mitochondrial mass and mitochondrial morphology dynamics in AD and MCI cybrid cell lines
Abstract:
Bioenergetic dysfunction occurs in Alzheimer's disease (AD) and mild cognitive impairment (MCI), a clinical syndrome that frequently precedes symptomatic AD. In this study, we modeled AD and MCI bioenergetic dysfunction by transferring mitochondria from MCI, AD and control subject platelets to mtDNA-depleted SH-SY5Y cells. Bioenergetic fluxes and bioenergetics-related infrastructures were characterized in the resulting cytoplasmic hybrid (cybrid) cell lines. Relative to control cybrids, AD and MCI cybrids showed changes in oxygen consumption, respiratory coupling and glucose utilization. AD and MCI cybrids had higher ADP/ATP and lower NAD+/NADH ratios. AD and MCI cybrids exhibited differences in proteins that monitor, respond to or regulate cell bioenergetic fluxes including HIF1α, PGC1α, SIRT1, AMPK, p38 MAPK and mTOR. Several endpoints suggested mitochondrial mass increased in the AD cybrid group and probably to a lesser extent in the MCI cybrid group, and that the mitochondrial fission-fusion balance shifted towards increased fission in the AD and MCI cybrids. As many of the changes we observed in AD and MCI cybrid models are also seen in AD subject brains, we conclude reduced bioenergetic function is present during very early AD, is not brain-limited and induces protean retrograde responses that likely have both adaptive and mal-adaptive consequences.
Insights
Alzheimer's disease (AD) and mild cognitive impairment (MCI) involve cellular energy problems. This study modeled these conditions, finding widespread bioenergetic dysfunction and adaptive cellular responses in early-stage AD and MCI.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Alzheimer's disease (AD) and mild cognitive impairment (MCI) are associated with bioenergetic dysfunction.
- MCI often precedes the symptomatic stages of AD, indicating early cellular changes.
Purpose of the Study:
- To model and characterize bioenergetic dysfunction in Alzheimer's disease (AD) and mild cognitive impairment (MCI) using cellular models.
- To investigate changes in cellular energy metabolism and related protein networks in AD and MCI.
Main Methods:
- Created cellular models (cybrids) by transferring mitochondria from platelet cells of control, MCI, and AD subjects into mtDNA-depleted SH-SY5Y cells.
- Assessed bioenergetic fluxes, including oxygen consumption, glucose utilization, and respiratory coupling.
- Analyzed key proteins involved in cellular energy regulation and mitochondrial dynamics (e.g., HIF1α, PGC1α, SIRT1, AMPK, p38 MAPK, mTOR).
Main Results:
- AD and MCI cybrids exhibited altered oxygen consumption, respiratory coupling, and glucose utilization compared to controls.
- Increased ADP/ATP ratios and decreased NAD+/NADH ratios were observed in AD and MCI cybrids.
- Changes in bioenergetics-regulating proteins and a shift towards increased mitochondrial fission were noted in AD and MCI cybrids.
Conclusions:
- Reduced bioenergetic function is a feature of early-stage AD and MCI, extending beyond the brain.
- Cellular models reveal complex retrograde responses to bioenergetic deficits, with potentially adaptive and maladaptive consequences.
- These findings highlight the critical role of bioenergetics in the pathogenesis of AD and MCI.
More Related Videos
08:15Exploring Mitochondrial Energy Metabolism of Single 3D Microtissue Spheroids Using Extracellular Flux Analysis
Published on: February 3, 2022
06:09Flow Cytometric Analysis of Multiple Mitochondrial Parameters in Human Induced Pluripotent Stem Cells and Their Neural and Glial Derivatives
Published on: November 8, 2021
