Determination of hair cell metabolic state in isolated cochlear preparations by two-photon microscopy

Abstract

It has been long recognized that mitochondria play a critical role in living cells by generating ATP, maintaining cellular redox potential, and detoxifying reactive oxygen species (ROS) and xenobiotics.¹ More recently, the roles of mitochondria in generating apoptotic signals and the permeability transition in acute necrotic injury have been described. Because of the high energy demands of neurons and the generation of high levels of ROS, the nervous system is particularly vulnerable to mitochondrial dysfunction. Mitochondria in neurons play significant roles in intracellular ${\mathrm{Ca}}^{2+}$ homeostasis by sequestering^{2, 3} ${\mathrm{Ca}}^{2+}$ and regulating synaptic transmission.⁴ In general, mitochondrial dysfunction can lead to a multisystem disorder that includes the central nervous system, peripheral nervous system, endocrine, cardiac, ocular, auditory, gastrointestinal, renal, myoskeletal, dermal, and hematological abnormalities. Progressive late onset mitochondriopathies are thought to be associated with age-related diseases and are based on diminished mitochondrial function due to progressive DNA damage (i.e., heteroplasmy) and deterioration of energy production.⁵