Subcellular resolution DO-SRS and 2PEF imaging of metabolic dynamics regulated by L-methionine in amyotrophic lateral sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a type of motor neuron disease that results in paralysis and death from a progressive loss of both upper and lower motor neurons. Emerging studies have indicated that excess production of reactive oxygen species (ROS) in dysfunctional mitochondria in addition to an inefficient antioxidant defense may contribute to the progression of the disease. L-methionine (Met) plays important roles in regulating cellular metabolism and activating endogenous antioxidant enzymes. We hypothesized that excess methionine treatment can provide ALS patients with an efficient antioxidant defense mechanism to control their disease. Here, we apply an optical imaging approach that combines deuterium oxide (D2O)-probed stimulated Raman scattering (DO-SRS) and two photon excitation fluorescence (2PEF) microscopies to directly image the effects of methionine-enriched diet on oxidative imbalance and cellular metabolism in neurodegenerative cells. Our preliminary data revealed that excess methionine increases syntheses of lipid and unsaturated lipid membranes. Meanwhile, the same diet decreases protein synthesis and oxidative imbalance. Our study suggests that excess methionine can provide a protective mechanism against oxidative imbalance and promote cellular repair in neurodegenerative diseases.