Characterization of Mitophagy in the Thyroid Gland: The Role of Diabetes Mellitus in hypothyroidism

• Grant number: 25/10324-5
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: August 25, 2025
• End date: October 25, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Tereza Nunes
• Grantee: Guilherme Rondi Fernandes
• Supervisor: Ian Ganley
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Dundee, Scotland
• Associated to the scholarship: 23/05869-7 - Role of pro-inflammatory cytokines in triggering hypothyroidism in experimental Diabetes Mellitus. Effect of T3 and insulin treatment, BP.IC

Abstract

The Thyroid Gland is known for its great burden of Reactive Oxygen Species (ROS), with minimal oxidative load being necessary for proper thyrocyte function, mainly in the form of H2O2 that is required for the synthesis of Thyroid Hormones (THs). Despite Antioxidant defenses (AOD), this increase in ROS is not inert, indeed thyroid cells show higher DNA damage than most. The literature extensively reports on the relevance of oxidative status to mitochondrial dynamics, such as the relation between mitochondrial ultrastructure and ROS. With that, it is highly possible that the reported increased damage and alterations also extend themselves to the mitochondria. However, the status of Mitochondrial Quality Control (MQC) in the thyroid gland is still poorly understood. In particular, few studies have directly assessed mitophagy (the autophagic recycling of damaged mitochondria). Even more scarce is the study of the effects of Diabetes Mellitus (DM) on thyroid mitophagy, despite previous studies on DM showing impaired MQC in many tissues, as is found in the retina of diabetic retinopathy. DM is considered the most prominent metabolic disease, while thyroid disorders are the second most prevalent. Previous studies have already shown that DM frequently correlates with thyroid disorders, with hypothyroidism being the most common but through as yet unknown etiology. Preliminary results show increased proinflammatory activity in the thyroid of alloxan-induced DM1 models, as well as altered mitochondrial respiration and differential expression of key fission and fusion proteins. Taken together, these data point to alterations on thyroid mitophagy brought on by DM - which may ultimately lead to the reported hypothyroidism. To this end, the present study aims to characterize the mitophagy taking place in the thyroid gland and assess the effects of DM on this process, giving insights into the development of hypothyroidism.PCCL3 rat thyroid follicular cells will be transduced to express the mito-QC reporter (mCherry-GFP-FIS1101-152) (mito-QC) and later subdivided in two experimental groups: Control (regular growth medium) and DM (growth medium with high glucose and lacking insulin, mimicking DM1). With that in mind, we hope to examine the effects of the pathophysiology of DM on the mitophagy of the thyroid gland.