Short ReviewAbsorption of monochromatic and narrow band radiation in the visible and near IR by both mitochondrial and non-mitochondrial photoacceptors results in photobiomodulation
Graphical abstract
Introduction
The majority of the cell chromophores including flavins, iron–sulfur centers or heme are localized in the mitochondria [1], thus light-cell interaction is essentially light-mitochondria interaction. Mitochondria, in addition to their main role as the cell powerhouse, play a pivotal role in apoptosis (Programmed Cell Death) by which many cells can precisely control the time of their own life/death. Moreover a variety of diseases have definitively been demonstrated to depend on mitochondrial functions; this then makes it possible that light irradiation with mitochondria can affect their pathophysiological function, and may perhaps be useful in therapy. In the last 30 years whether and how light can affect mitochondria has been investigated. Indeed, in photobiomodulation (historical terms: low level light therapy – LLLT, laser phototherapy) use is currently made of both monochromatic [laser] and narrow band (LED) light in the optical spectral region at ∼600–∼900 nm (we will refer to this as L-LED) to treat in a nondestructive and non-thermal manner a variety of biological targets [2], [3], [4]. As a result of L-LED irradiation stimulation of neuronal growth and of DNA and RNA synthesis, retinoprotective effects, post-ischemia cardiomyocyte protective effects, promotion of cell adhesion, improved neurological function post-traumatic brain injury and stroke, acceleration of wound healing, cellular and extracellular matrix proliferation, collagen production and granulation tissue formation, and reduction of the inflammatory response were found [3], [4]. Thus it may be that it is time to consider photobiomodulation as a drug equivalent [5].
Despite the fact that many investigations have been carried out on photobiostimulation, no clear-cut results have been obtained on the mechanisms responsible for the beneficial effects, and in particular on the role played by mitochondria [6].
Therefore, although a variety of hypotheses has been put forward to explain the light dependent effects, a reasonable skepticism still exists regarding the concept of photobiostimulation within the medical community. Indeed the complexity of rationally choosing among a large number of irradiation parameters including coherence, wavelength, fluence, fluence, treatment timing, etc. has led to the publication of some negative studies.
In particular the question arises as to whether some effects resulting from light irradiation are mediated by the mitochondrial photosensitivity and/or to whether some biomolecules themselves located in mitochondria and/or in other cell compartments, can be themselves targets of light with a consequent modification of their biochemical features. Thus the possibility arises that L-LED-mitochondria interaction could involve both primary and secondary mechanisms both of them leading to multifaceted effects e.g. wound healing, pain modulation, etc. [7].
In this connection the photobiological fundamentals of low-power laser therapy are in http://www.equilibretechnologies.fr/IMG/pdf/PHOTOBIOLOGICAL_FUNDAMENTALS_OF_LOW-jpg.pdf: the assumption in this survey was that photon absorption modifies the molecular configuration of the photoacceptor/s with a resulting alteration of its/their own properties with the possible consequence of a signaling cascade/s.
We will review papers on mitochondria/biomolecule-L-LED interaction with the aim of (i) showing whether and how mitochondrial structure and function can change as a result of light irradiation; (ii) giving some information on the interaction between L-LED and some biomolecules, present both in mitochondria and in other cell components, commonly not expected to be light targets.
Section snippets
How the effect of light irradiation on biological systems can be investigated
With the aim of encouraging further investigation, in this section we will briefly describe methods used in the study of the interaction of L-LED with mitochondria and other biological systems.
In a typical experiment (Fig. 1), either laser or narrow band light (in this case both low power He–Ne laser with λ = 632.8 nm, and non-coherent red light LED λ = 650 ± 20 nm, were used) is directed at the biological sample consisting of cells, cell homogenates mitochondria, mitochondrial fractions, biomolecules,
The effect of monochromatic and narrow band radiation in the visible and near IR on mitochondrial structure
The effect of monochromatic and narrow band radiation in the visible and near IR on the structure of mitochondria has been investigated with mitochondria from a variety of sources; these studies will be described separately. A survey of L-LED biological system interaction leading to both structural and functional modifications is reported in Table 1, Table 2.
Mitochondrial function and monochromatic and narrow band radiation in the visible and near IR
As expected, since mitochondrial function and structure are related each other [30], in addition to modification of their structure, irradiation of mitochondria with L-LED can also result in modification of their main function, namely oxidative phosphorylation. Moreover, certain of their biosynthetic properties are also affected.
Cytochrome c oxidase is the main mitochondrial photoacceptor
To gain some insight into the mechanism by which L-LED irradiation result in photobiostimulation, in Karu’s laboratory the action spectra for DNA and RNA synthesis rate in cultured cell and that of cell adhesion were investigated [69], [70]. The spectra showed four strict maxima at 620, 680, 760 and 820 nm which were identified as belonging to one of the intermediate forms of the cytochrome c oxidase redox cycle [71], [72]. Since there is a partial overlapping of the bands of the action spectrum
Enzymes
That in addition to cytochrome c oxidase other enzymes could be targets of low power light was shown in a series of pioneering investigations by Bolognani et al. who showed that arylsulphatase, lactate dehydrogenase, myosin ATPase, acid phosphatase, creatine kinase and lactate dehydrogenase are sensitive to light: in most cases irradiation resulted in reactivation of previously inactivated enzymes [94], [95], [96]. Moreover, the findings of Lombard and Rossetti [97] and Rossetti et al. [98]
Conclusions and perspectives
Although there is general consensus of the occurrence of photobiostimulation to date the elucidation of the mechanism by which the light-biological target interaction results in photobiostimulation still remains a challenge for the researchers working in this field. Nonetheless some achievements have been undertaken.
- 1.
The main scenario remains that first proposed in 1988 by Karu [74] and later substantiated [72]: photoexcitation induces changes in the activity of the cytochrome c oxidase, the
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