Sdhc, short for succinate dehydrogenase complex subunit C, is one of the components of mitochondrial complex II. It anchors the catalytic subunits SDHA and -B in the inner mitochondrial membrane, playing a crucial role in the citric acid cycle. Dysfunction in Sdhc can disrupt normal cellular energy metabolism and is associated with various biological processes and disease development [2].

Germline pathogenic variants in Sdhc are one of the causes of inherited phaeochromocytomas/paragangliomas. A retrospective survey estimated penetrance for symptomatic tumours in Sdhc mutation carriers. By Kaplan-Meier analysis, the penetrance in non-probands with Sdhc mutations by age 60 years was estimated [1]. A UK-wide case series reported 91 Sdhc cases, with head and neck paraganglioma being the most common tumour type. Cumulative tumour risk at age 60 years was 0.94 in probands and 0.16 in non-probands [3]. In colorectal cancer, downregulation of Sdhc is associated with poor prognosis and promotes metastasis by reprogramming fatty acid metabolism through the PI3K/AKT signaling pathway [4].

In conclusion, Sdhc is essential for mitochondrial function and energy metabolism. Its dysregulation, often through genetic variants, is associated with an increased risk of various tumours, including phaeochromocytomas, paragangliomas, and colorectal cancer. Understanding Sdhc's role through research on mutation carriers helps in better counselling affected families and developing personalized management strategies [1,3].