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Electrical Stimulation Mimics Endurance Exercise‐induced Autophagy in Skeletal Muscle

Autophagy, a cellular recycling process, plays a crucial role in maintenance of cellular function, and has emerged as a potential therapeutic strategy in chronic adult diseases such as diabetes and cancer. While muscle contraction by endurance exercise is known to cause autophagy, whether muscle contraction induced by electrical stimulation (ESTIM) can mimic an exercise effect remains unknown. Here we showed that four weeks of ESTIM (40 min/day, four days/week) upregulate autophagy flux. Four healthy female subjects, aged 18–24 years participated in the study. Prior to and post ESTIM, muscle samples were collected by a needle biopsy from quadriceps of dominant (control) and non‐dominant legs (experiment), onto which ESTIM was applied, respectively. Our data demonstrated that ESTIM significantly increased autophagic flux as evidenced by an increase in the ratio of LC3II to LC3I and LC3II levels, as well as a decline in P62 levels. Intriguingly, ESTIM‐mediated autophagy coincided with Beclin‐1 and Atg7 downregulation, whereas upregulation of BNIP3, a strong autophagy promoter ensued in response to ETIM compared to untreated muscles. Also, HSP70 reported to be a lysosome function enhancer arose by ESTIM. We assessed if ESTIM results in mitochondrial biogenesis and observed that, despite a significant decline in levels of PGC‐1α and NFR‐1, ESTIM exhibited enhanced levels of mitochondrial complex II (SDHB) in parallel with a mitochondrial transcription factor, TFAM. Taken together, our results suggest for the first time that chronic ESTIM induces autophagy in the absence of upregulation of Beclin1 and Atg7, but in the presence of BNIP3. Furthermore, ESTIM may be an important therapeutic approach that can imitate an exercise effect with regard to mitochondrial biogenesis.