Relationship between low molecular weight beta-amyloid peptide-induced fission/fusion imbalance and mitochondrial functions

Abstract

Mitochondria are involved in various vital cellular functions, ranging from bioenergetic metabolism, Ca2+ homeostasis to regulation of apoptosis. Dysfunction of mitochondria is a prominent feature in neurodegenerative diseases such as Alzheimer’s disease (AD); however the underlying mechanism of how the organelle becomes defected remains elusive. Mitochondria are dynamic organelles which continuously undergo fission and fusion to regulate their morphology and distribution. Recently, imbalance of fission/fusion has been suggested to be a novel mechanism of neurodegeneration. Nonetheless, the relationship between fission/fusion imbalance and functions of mitochondria is unclear. In the present study, we hypothesize that an imbalance of fission/fusion would result in mitochondrial dysfunction. We aim to investigate the temporal relationship between low molecular weight β-amyloid peptide (LMW Aβ)-induced impairment of mitochondrial dynamics and mitochondrial functions using different parameters. We found that LMW Aβ induced a time-dependent change in mitochondrial morphology. The length of mitochondria of hippocampal neurons treated with LMW Aβ was significantly shorter than that in control. Mitochondria changed from a long tubular network to rod-shaped and fragmented, implicating that the normal fission/fusion balance is disrupted. Different aspects of mitochondrial function were monitored at the corresponding Aβ treatment time-points using different parameters, e.g. mitochondrial superoxide production, mitochondrial Ca2+ concentration and mitochondrial membrane potential. The current study provides new insights of how mitochondrial dynamics is involved in neurodegeneration in AD.