**1. Introduction**

Fatty acid oxidation (FAO) provides the major source of energy supply for skeletal muscles in situations requiring simultaneous glucose sparing, and major energy supply, such as prolonged fasting or exercise. ß-oxidation is the main pathway of fatty acid catabolism in mitochondria [1]. The accumulation of oversupplied fatty acids (FAs) in different tissues, such as the pancreas, liver, and skeletal muscle, might lead to a cellular dysfunction in these tissues, and an apoptotic cell death, commonly referred to as "lipotoxicity" [2,3]. The toxic effects of FAs seem to be dependent on their chain length and degree of saturation. The two-common long-chain saturated FAs (SFA), palmitate (C16:0) and stearate (C18:0), are known to be the most lipotoxic ones. In contrast, monounsaturated FAs such as oleate (C18:1), have been reported to protect against the above-mentioned SFA-induced toxicity [2,4]. Moreover, saturated FAs have worsened the insulin-resistance, while monounsaturated and polyunsaturated ones improved it [5].

The effect of temperature on the functional properties of skeletal rat muscle mitochondria was reported in one study [6]. Increasing the assay temperature in above-mentioned study within the range of 25–42 ◦C increased the mitochondrial respiratory chain activities, resulting in an elevated phosphorylation rate. They reported a temperature-induced decrease in oxidative phosphorylation (OXPHOS) efficiency as well.

It has been shown that the increase of temperature from 35 ◦C to 40 ◦C induced the uncoupling of substrate oxidation from adenosine diphosphate (ADP) phosphorylation, and decreased the efficiency of mitochondria to produce adenosine triphosphate (ATP) in skeletal myofibers. This uncoupling effect was more pronounced for FAs than for carbohydrates as substrate [7]. It is already known that a reduction in substrate oxidation, caused by mitochondrial dysfunctions, leads to a lipid accumulation, such as the deposition of lipid mediators, such as diacylglycerols (DAG) and ceramides (CER). Both, DAG and CER are reported to inhibit insulin signaling [8–10].

The m.3243A>G point mutation in the *MT-TL1* gene (encoding mt-tRNALeu(UUR)) can be found in approximately 80% of patients with mitochondrial encephalopathy, lactic acidosis, and stroke like episodes (MELAS)-syndrome. In these patients, the ATP production rate was significantly less than in controls [11] and the mitochondrial respiration is known to be impaired [12]. Diabetes mellitus frequently accompanies the m.3243A>G mutation [13]. Thus, the evaluation of effects of saturated free fatty acids (FFAs), which could lead to an insulin resistance, might be relevant for these patients.

The aim of the present study was to evaluate the oxidative phosphorylation and ß-oxidation pathway in patients harboring the m.3243A>G mutation. It was of interest to examine whether palmitate and oleate show a toxic or protective effect on OXPHOS in myoblasts of patients with the m.3243A>G mutation. Moreover, the effect of a fever-stimulating temperature on ß-oxidation was simulated in 40 ◦C cultured cells in both, m.3243A>G patients and controls.
