title: Cardiac Kinetophagy Coincides with Activation of Anabolic Signaling.
abstract: OBJECTIVE
  Growing evidence has shown that endurance exercise is a strong inducer of autophagy in various tissues. Thus, we define here endurance exercise-induced autophagy as "kinetophagy" derived from the Greek terms "kineto" (movement), "auto" (self), and "phagy" (eating). Currently, the exact cellular mechanisms responsible for kinetophagy remain unclear; hence, we examined kinetophagy signaling transduction pathways occurring during acute endurance exercise (AEE).
  
  
  METHODS
  C57BL/6 mice were randomly assigned to either AEE (n = 7) or control sedentary group (CON, n = 7). After 5 d of treadmill running acclimation, mice performed 60 min of a single bout of treadmill running at 12 m · min(-1) on a 0% grade. Hearts were excised immediately 1 h after exercise and homogenized for Western blot analyses.
  
  
  RESULTS
  Our data showed that AEE promoted kinetophagy flux (an increase in LC3-II to LC3-I ratio and LC3-II levels and a reduction in p62 levels) with Beclin-1 levels suppressed but Atg7 levels elevated compared with those in the sedentary group. We also observed that AEE increased lysosome-associated membrane protein and cathepsin L, linked to the termination process of autophagy, and that AEE augmented potent autophagy inducers (i.e., adenosine monophosphate kinase phosphorylation, BNIP3, and HSP70). Moreover, we found that exercise-mediated BNIP3 upregulation is associated with hypoxia-inducing factor 1α rather than FoxO3a. Intriguingly, we found for the first time that kinetophagy parallels with anabolic signaling activation (Akt and mammalian target of rapamycin).
  
  
  CONCLUSIONS
  Our findings provide evidence that AEE results in kinetophagy without a time-associated elevation in Beclin-1 but with the presence of Akt-mTOR activation and that AEE-induced activation of anabolic signaling is not associated with kinetophagy promotion.
authors.affiliation: 1Molecular and Cellular Exercise Physiology Laboratory, Department of Exercise Science, University of West Florida, Pensacola, FL; 2Exercise Biochemistry Laboratory, Korea National Sport University, Seoul, SOUTH KOREA; 3Department of Biology, University of West Florida, Pensacola, FL; and 4Department of Physical Sciences, Alabama State University, Montgomery, AL.
authors.forename: Youngil
authors.initials: Y
authors.lastname: Lee
authors.forename: Eun-Bum
authors.initials: EB
authors.lastname: Kang
authors.forename: Insu
authors.initials: I
authors.lastname: Kwon
authors.forename: Ludmila
authors.initials: L
authors.lastname: Cosio-Lima
authors.forename: Peter
authors.initials: P
authors.lastname: Cavnar
authors.forename: Gulnaz T
authors.initials: GT
authors.lastname: Javan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D056668:Cathepsin L / Q000378:metabolism; D004789:Enzyme Activation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D051907:Lysosomal Membrane Proteins / Q000096:biosynthesis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011897:Random Allocation; D012420:Running / Q000502:physiology*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000502:physiology; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; C502661:Atg7 protein, mouse; C508686:BNip3 protein, mouse; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D018840:HSP70 Heat-Shock Proteins; D051907:Lysosomal Membrane Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D056668:Cathepsin L; C534278:Ctsl protein, mouse; D000071193:Autophagy-Related Protein 7