Inclusion Criteria (Mitochondrial Disease Patients):
* Males and females, between the ages of 7 and 75, inclusive
* Suspected (based on clinical presentation) or definite genetic mitochondrial disease diagnosis (i.e., genetic mutations in the constituents of the mitochondrial respiratory chain and/or genetic mutations that are likely to affect mitochondrial function)
* Clinically eligible for an MRI of the lower leg. We are conducting clinical leg MRI scans of patients with definite mitochondrial disease for indications that include muscle weakness and muscle fatigue.
* Able to perform sub-maximal ankle dorsiflexion leg exercise during the MRI study
Inclusion Criteria (Healthy Controls):
* Males and females, between the ages of 7 and 75 years, inclusive
* Able to perform sub-maximal ankle dorsiflexion leg exercise during the MRI study
Inclusion Criteria (Evaluable Healthy Controls and Cases for Data Analysis):
* To note, we will merge coded datasets from Institutional Review Board (IRB) #15-012445, IRB #16-013364, and IRB #08-006177 with data from this study as part of our data analysis plan.
* Complete and evaluable healthy control and cases from IRB #15-012445, IRB #16-013364, and IRB #08-006177
Exclusion Criteria (Mitochondrial Disease Patients and Healthy Controls):
* In the investigator's opinion, inability to fully comply with research procedures
* Active alcohol and/or substance abuse, including tobacco-use
* A pacemaker; any metal-based medical or non-medical devices/implants; any non-removable metal-based object (e.g., body piercings, jewelry, etc.) that cannot be cleared through radiologic evaluation
* Any history of intraocular injury or fragment in or around the orbit that cannot be cleared through radiologic evaluation
* Any history of bullet, shrapnel, or stabbing wounds that cannot be cleared through radiologic evaluation
* Past or current employment involving (or exposure to) a metal grinder (e.g., at a construction worksite)
* Claustrophobia or any known medical conditions which can be exacerbated by stress, anxiety, or panic attacks triggered by enclosed spaces
* Any potentially interfering clinical MRI contrast agents, as reviewed with the radiology team
* At the discretion of the principal investigator (PI), any medical condition that will interfere with or prevent the safe completion of the study
* Any female participant with childbearing potential who is knowingly pregnant or suspects that she is pregnant will be removed from the study. (Although there are no known risks of MRI on pregnant females or fetuses, there is a possibility of yet undiscovered pregnancy-related risks. Since there is no direct benefit from participating in this protocol for pregnant females, they will be excluded to ensure their long-term safety and that of their unborn fetus.)
* To note, for this protocol, participants are instructed to lie still in the MRI scanner; there is no contrast or sedation. Participants will be asked to perform a brief (\< 2 minute) foot-pedal exercise. Investigators will ensure that total MRI scanning time (i.e., clinically indicated and study-specific scanning) does not exceed 120 minutes within a single day. Participants who do not possess the cognitive and/or physical abilities to perform these procedures will not be included.
Exclusion Criteria (Healthy Controls)
* Any history or genetic confirmation of mitochondrial disease
