Mitochondrial Modulators: The Defender

Abstract

Mitochondria are widely considered the "power hub" of the cell because of their pivotal roles in energy metabolism and oxidative phosphorylation. However, beyond the production of ATP, which is the major source of chemical energy supply in eukaryotes, mitochondria are also central to calcium homeostasis, reactive oxygen species (ROS) balance, and cell apoptosis. The mitochondria also perform crucial multifaceted roles in biosynthetic pathways, serving as an important source of building blocks for the biosynthesis of fatty acid, cholesterol, amino acid, glucose, and heme. Since mitochondria play multiple vital roles in the cell, it is not surprising that disruption of mitochondrial function has been linked to a myriad of diseases, including neurodegenerative diseases, cancer, and metabolic disorders. In this review, we discuss the key physiological and pathological functions of mitochondria and present bioactive compounds with protective effects on the mitochondria and their mechanisms of action. We highlight promising compounds and existing difficulties limiting the therapeutic use of these compounds and potential solutions. We also provide insights and perspectives into future research windows on mitochondrial modulators.

Keywords: compounds; mitochondria diseases; mitochondria dysfunction; mitochondria health.

Figure 1

Comparison between healthy and dysfunctional mitochondria, highlighting the key mechanisms of mitochondrial dysfunction. ETC: Electron transport chain; ROS: Reactive oxygen species.

Figure 2

OXPHOS pathway, showing the transfer of electrons in the ETC to produce ATP. NADH: Reduced nicotinamide adenine dinucleotide; FADH: Reduced flavin adenine dinucleotide; ADP: Adenosine diphosphate; ATP: Adenosine triphosphate.

Figure 3

Chemical structures of flavonoids.

Figure 4

Chemical structures of other phenolic compounds apart from flavonoids.

Figure 5

Chemical structures of alkaloids.

Figure 6

Chemical structures of terpenes.

Figure 7

Other structural classes. Organosulphur compounds: 44-46; benzochromone: 47; Amine: 48; Lactone: 49; Cyclic polyketide: 50; Coumarin derivative: 51, Organic acid: 52.

Figure 8

Chemical Structures of synthetic mitochondrial modulators.

Figure 9

(a) Distribution of compounds across various structural classes of flavonoids, phenolic compounds, alkaloids, terpenes, other structural classes, and synthetic compounds. (b) Distribution of compounds across various targets, including ROS, apoptosis, biogenesis, respiratory chain complexes, ATP, and mitochondrial morphology.