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The mitochondrion is a highly dynamic organelle that is critical for energy production and numerous metabolic processes. Drosophila Chchd2, a homolog of the human disease-related genes CHCHD2and CHCHD10, encodes a mitochondrial protein. In this study, we found that loss of Chchd2in flies resulted in progressive degeneration of photoreceptor cells and reduced muscle integrity. In the flight muscles of adult Chchd2mutants, some mitochondria exhibited curling cristae and a reduced number of cristae compared to those of controls. Overexpression of Chchd2 carrying human disease-related point mutations failed to fully rescue the mitochondrial defects in Chchd2mutants. In fat body cells, loss of Chchd2resulted in fragmented mitochondria that could be partially rescued by Marfoverexpression and enhanced by Opa1 RNAi. The expression level of Opa1 was reduced in Chchd2mutants and increased when Chchd2was overexpressed. The chaperone-like protein P32 co-immunoprecipitated with Chchd2 and YME1L, a protease known to processes human OPA1. Moreover, the interaction between P32 and YME1L enhanced YME1L activity and promoted Opa1 degradation. Finally, Chchd2 stabilized Opa1 by competing with P32 for YME1L binding. We propose a model whereby Chchd2 regulates mitochondrial morphology and tissue homeostasis by fine-tuning the levels of OPA1.

Thyroid cancer (TC) is the most predominant malignancy of the endocrine system, with steadily growing occurrence and morbidity worldwide. Although diagnostic and therapeutic methods have been rapidly developed in recent years, the underlying molecular mechanisms in the pathogenesis of TC remain enigmatic. The N6-methyladenosine(m6A) RNA modification is designed to impact RNA metabolism and further gene regulation. This process is intricately regulated by a variety of regulators, such as methylases and demethylases. Aberrant m6A regulators expression is related to the occurrence and development of TC and play an important role in drug resistance. This review comprehensively analyzes the effect of m6A methylation on TC progression and the potential clinical value of m6A regulators as prognostic markers and therapeutic targets in this disease.