Heidler 2013 Abstract MiP2013

Heidler J, Wittig I, Henze D, Krüger C, Kostin S, Braun T, Szibor M (2013) Functional plasticity of interfibrillary mitochondria (IFM) as cardiac response mechanism to stress

Link: MiP2013

Heidler J, Wittig I, Henze D, Krüger C, Kostin S, Braun T, Szibor M (2013)

Event: MiP2013

A morphological hallmark of the failing human heart is a devastative autophagic deg-radation of cellular structures starting from the perinuclear region, proposed to actively shift the heart into a decompensated state [1]. We studied heart samples from different species, i.e. a mouse model of cardiac specific expression of MCP1 that autonomously develops heart failure [2], hibernating Syrian hamsters [3] and a pig model of mitochondrial dysfunction exposed to hyperbaric oxygen.

Our data reveal an age-dependent increase of perinuclear degradation in mouse hearts that occurred prior to the onset of cardiac dysfunction. These center core-like lesions in the myofibrillar compartment are most likely the end-stage result of a vicious cycle that starts with a physiological response to lowered levels of cardiac workload. Accordingly we found that in hibernating Syrian hamsters under conditions of depressed metabolism intrafibrillary mitochondria are reversibly silenced whilst subsarcolemmal mitochondria remain more active. Central remodeling of cardiomyocyte compartments is a phenomenon primarily known in the hibernating myocardium (4). Here we show in pig hearts that the isolated impairment of the interfibrillary compartment can be fully re-activated upon treatment with hyperbaric oxygen.

We conclude that differential compartment regulation by switching the activity status of mitochondrial sub-populations from on to off and vice versa might provide a hitherto unnoticed flexible on-demand plasticity in cardiomyocytes. Such alterations make proper myofibril contraction in the silenced compartment unlikely. Silenced mitochondria can be re-activated on demand. Only long-lasting mitochondrial silencing, e.g. upon chronic cardiac overload, might increase the risk of adverse cardiomyocyte remodeling.

1.  Hein S, Arnon E, Kostin S, Schönburg M, Elsässer A, Polyakova V, Bauer EP, Klövekorn W-P, Schaper J (2003) Progression from compensated hypertrophy to failure in the pressure-overloaded human heart: structural deterioration and compensatory mechanisms. Circulation 107: 984–991.
2.  Kolattukudy PE, Quach T, Bergese S, Breckenridge S, Hensley J, Altschuld R, Gordillo G, Klenotic S, Orosz C, Parker-Thornburg J (1998) Myocarditis induced by targeted expression of the MCP-1 gene in murine cardiac muscle. Am J Pathol 152: 101–111.
3.  Toole L, Belai A, Shochina M, Burnstock G (1999) The effects of hibernation on the myenteric plex-us of the golden hamster small and large intestine. Cell and Tissue Research 296: 479–487.
4.  Borgers M, Ausma J (1995) Structural aspects of the chronic hibernating myocardium in man. Basic Res Cardiol 90: 44–46.

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