The ADCK Kinase Family: Key Regulators of Bioenergetics and Mitochondrial Function and Their Implications in Human Cancers

Abstract

AarF domain-containing kinases (ADCKs) are a family of putative mitochondrial proteins that have been implicated in various aspects of mitochondrial function and cellular metabolism. Mitochondria play a crucial role in cellular bioenergetics, primarily in adenosine triphosphate (ATP) production, while also regulating metabolism, thermogenesis, apoptosis, and reactive oxygen species (ROS) generation. Evidence suggests that the ADCK family of proteins is involved in maintaining mitochondrial architecture and homeostasis. In detail, these proteins are believed to play a role in processes such as coenzyme Q biosynthesis, energy production, and cellular metabolism. There are five known isoforms of ADCK (ADCK1-ADCK5), some of which have similar activities, and each also has its own unique biological functions. Dysregulation or mutations in specific ADCK isoforms have been linked to several pathological conditions, including multiple human cancers, primary coenzyme Q10 (CoQ10) deficiency, and metabolic disorders. This review surveys the current body of peer-reviewed research on the ADCK protein family, incorporating data from the primary literature, case studies, and experimental studies conducted in both in vitro and in vivo systems. It also draws on existing review articles and known published findings to provide a comprehensive overview of the functional roles, disease associations, and molecular mechanisms of ADCK proteins. Further in-depth research on ADCK proteins has the potential to unlock critical insights into their precise mechanisms. This could pave the way for identifying new therapeutic targets for mitochondrial and metabolic-related diseases, as well as for advancing cancer treatment strategies.

Keywords: ADCK1; ADCK2; ADCK3; ADCK4; ADCK5; bioenergetics; human cancer; mitochondria.

Figure 1

ADCK family functions. Distinct yet overlapping roles of ADCK family members (ADCK1–ADCK5) in cellular homeostasis and tumorigenesis. The ADCK kinases are involved in a variety of mitochondrial functions, including coenzyme Q (CoQ) biosynthesis, mitochondrial dynamics, and energy production. ADCK1 is implicated in mitochondrial fusion/fission dynamics, lipid homeostasis, apoptosis, ATP production, ROS production, and metastasis. ADCK2 contributes to CoQ biosynthesis, lipid regulation, superoxide generation, inflammatory signaling, and cell cycle progression. ADCK3 is associated with CoQ biosynthesis, ROS production, immune evasion, and cancer progression. ADCK4 participates in tumor modulation, CoQ biosynthesis, lysosomal remodeling, and ROS regulation and exhibits kinase activity. ADCK5 is linked to oxidative stress response, mitochondrial homeostasis, immune regulation, drug resistance, and cellular invasion. Collectively, the ADCK family modulates key processes underlying oncogenesis, metabolic adaptation, immune signaling, and mitochondrial integrity, highlighting their potential as diagnostic markers and therapeutic targets in a range of pathological contexts. Created in BioRender. Jacquet, N. (2025) https://BioRender.com/bt89fbt (accessed on 8 June 2025).