An overview of response pathways for protection of mitochondria from protein misfolding stress

Abstract

Mitochondria are canonically known as cellular powerhouse but apart from ATP production, these organelles are hubs of critical metabolic and cellular pathways like fatty acid metabolism, calcium signalling, heme biosynthesis, and apoptosis. Mitochondrial proteome contains almost 1500 proteins to facilitate these cellular processes; however, maintaining a healthy mitochondrial proteome is an extremely challenging task. As mitochondria are continuously exposed to various cellular stresses, misfolding and aggregation of proteins is one of the most prominent outcomes of these stresses, protein misfolding inside the mitochondria or on the mitochondrial surface poses a severe threat to mitochondrial health as well as to cellular health. To cope with such proteotoxic stress, cells have evolved multiple stress response pathways, which help in the maintenance of healthy mitochondrial proteome, resulting in prolonged cellular survival. Here in this review, we have summarized the origin of mitochondrial proteotoxicity and cellular response to tackle these toxic proteins.