In our study, we developed a pipeline to integrate single-molecule real-time sequencing (SMRT-seq) with comprehensive metabolic phenotyping to examine reduced mitochondrial respiration in the skeletal muscle of individuals with type 2 diabetes. SMRT-seq revealed ∼67,000 isoforms originating from ∼14,000 unique genes; the isoform numbers per gene did not differ between participants with diabetes and matched control participants. Our data identified novel alternative splicing events, including two variants of the ATP5F1A gene encoding a subunit for ATP synthase. Among these, two novel transcripts were expressed exclusively in control participants. Our findings link transcriptomic changes to impaired mitochondrial respiration in type 2 diabetes, with the potential of providing novel therapeutic targets to improve metabolic health.
Schön et al. (Wed,) studied this question.